Nathaniel Fillmore was the son of Nathaniel Fillmore Sr. (1739-1814), a native of Franklin, Connecticut who became one of the earliest settlers of Bennington when it was founded in the territory then called the New Hampshire Grants. Nathaniel Fillmore Sr. was a member of the Green Mountain Boys, and served as an ensign and first lieutenant during the American Revolution. In 1767, Nathaniel Fillmore Sr. married Hepzibah Wood (1747-1783), the mother of Nathaniel Fillmore and grandmother of Millard Fillmore.

Nathaniel Fillmore and Phoebe Millard moved from Vermont in 1799, seeking better opportunities than were available on Nathaniel's stony farm, but the title to their Cayuga County land proved defective, and the Fillmore family moved to nearby Sempronius, where they leased land as tenant farmers, and Nathaniel occasionally taught school. Historian Tyler Anbinder described Fillmore's childhood as, “...one of hard work, frequent privation, and virtually no formal schooling".

Millard Fillmore was born January 7, 1800 in a log cabin, on a farm in what is now Moravia, Cayuga County, in the Finger Lakes region of New York state. His parents were Phoebe (Millard) and Nathaniel Fillmore—he was the second of eight children and the oldest son.

Fillmore was a staunch opponent of European influence in Hawaii. France under Napoleon III sought to annex Hawaii, but backed down after Fillmore issued a strongly worded message warning that "the United States would not stand for any such action." Taylor had pressed Portugal for payment of American claims dating as far back as the War of 1812, and had refused offers of arbitration; Fillmore gained a favorable settlement.

Later in 1819, Nathaniel moved the family to Montville, a hamlet of Moravia. Appreciating his son's talents, Nathaniel persuaded Judge Walter Wood, the Fillmores' landlord and the wealthiest person in the area, to allow Millard to be his law clerk for a trial period. Wood agreed to employ young Fillmore, and to supervise him as he read law. Fillmore earned money teaching school for three months and bought out his mill apprenticeship. He left Wood after 18 months—the judge paid him almost nothing, and the two quarreled after Fillmore, unaided, earned a small sum advising a farmer in a minor lawsuit. Refusing to pledge not to do it again, Fillmore gave up his clerkship. Nathaniel again moved the family, and Millard accompanied them west to East Aurora, in Erie County, near Buffalo., where Nathaniel purchased a farm which became prosperous.

In 1821, Fillmore turned 21 and reached emancipation. He taught school in East Aurora, and accepted a few cases in justice of the peace courts, which did not require the practitioner to be a licensed attorney. He moved to Buffalo the following year and continued his study of law—first while teaching school, and then in the law office of Asa Rice and Joseph Clary. At that time he also became engaged to Abigail Powers. In 1823, he was admitted to the New York bar, declined offers from Buffalo law firms, and returned to East Aurora to establish a practice as the town's only residing Lawyer. Later in life, Fillmore stated that he initially lacked the self-confidence to practice in the larger city of Buffalo; his biographer, Paul Finkelman, suggested that after being under others' thumbs all his life, Fillmore enjoyed the independence of his East Aurora practice. On February 5, 1826, Millard and Abigail wed, and later had two children, Millard Powers Fillmore (1828–1889) and Mary Abigail Fillmore (1832–1854).

Many Anti-Masons were opposed to the presidential candidacy of General Andrew Jackson, a Mason, and Fillmore was a delegate to the New York convention that endorsed President John Quincy Adams for re-election, and served as well at two Anti-Masonic conventions in the summer of 1828. At the conventions, Fillmore and one of the early political bosses, newspaper Editor Thurlow Weed, met and impressed each other. By then, Fillmore was the leading citizen in East Aurora, successfully sought election to the New York State Assembly, and served in Albany for three one-year terms (1829 to 1831). Fillmore's 1828 election was in contrast to the victories of the Jacksonian Democrats (soon the Democrats), who swept the general into the White House and their party to a majority in Albany—thus Fillmore was in the minority in the Assembly. He proved effective anyway, promoting legislation to provide court witnesses the option of taking a non-religious oath, and in 1830 abolishing imprisonment for debt. By then, much of Fillmore's legal practice was in Buffalo and later that year he moved there with his family; he did not seek re-election in 1831.

In Washington, Fillmore urged the expansion of Buffalo harbor, a decision under federal jurisdiction, and privately lobbied Albany for the expansion of the state-owned Erie Canal. Even during the 1832 campaign, Fillmore's affiliation as an Anti-Mason had been uncertain, and he rapidly shed the label once sworn in. Fillmore came to the notice of the influential Massachusetts senator Daniel Webster, who took the new congressman under his wing. Fillmore became a firm supporter and the close relationship between the two would continue until Webster's death late in Fillmore's presidency. Despite Fillmore's support of the Second Bank as a means of national development, he did not speak in the congressional debates in which some advocated renewing its charter, although Jackson had previously vetoed legislation for a charter renewal. Fillmore supported building infrastructure, voting in favor of constructing a bridge across the Potomac River and navigation improvements on the Hudson.

Anti-Masonry was still strong in Western New York though it was petering out nationally, and when the Anti-Masons did not nominate him for a second term in 1834, Fillmore declined the Whig nomination, seeing that the two parties would split the anti-Jackson vote and elect the Democrat. Despite Fillmore's departure from office, he was a rival for state party leadership with Seward, the unsuccessful 1834 Whig gubernatorial candidate. Fillmore spent his time out of office building his law practice and boosting the Whig Party, which gradually absorbed most of the Anti-Masons. By 1836, Fillmore was confident enough of anti-Jackson unity that he accepted the Whig nomination for Congress. Democrats, led by their presidential candidate, Vice President Martin Van Buren, were victorious nationwide and in Van Buren's home state of New York, but Western New York voted Whig and sent Fillmore back to Washington.

Van Buren, faced with the economic Panic of 1837, caused in part by lack of confidence in private bank note issues after Jackson had instructed the government to only accept gold or silver, called a special session of Congress. Government money had been held in so-called "pet banks" since Jackson had withdrawn it from the Second Bank; Van Buren proposed to place funds in sub-treasuries, government depositories that would not lend money. Believing that government funds should be lent to develop the country, Fillmore felt this would lock the nation's limited supply of gold money away from commerce. Van Buren's sub-treasury and other economic proposals passed, but as hard times continued, the Whigs saw an increased vote in the 1837 elections, and captured the New York Assembly. This set up a fight for the 1838 gubernatorial nomination. Fillmore supported the leading Whig vice presidential candidate from 1836, Francis Granger; Weed preferred Seward. Fillmore was embittered when Weed got the nomination for Seward, but campaigned loyally; Seward was elected, while Fillmore won another term in the House.

The rivalry between Fillmore and Seward was affected by the growing anti-slavery movement. Although Fillmore disliked slavery, he saw no reason it should be a political issue. Seward, on the other hand, was hostile to slavery and made that clear in his actions as governor, refusing to return slaves claimed by Southerners. When the Buffalo bar in 1839 proposed Fillmore for the position of vice chancellor of the eighth judicial district, Seward refused, and nominated Frederick Whittlesey—indicating that if the state senate rejected Whittlesey, he still would not appoint Fillmore.

Fillmore was active in the discussions of presidential candidates that preceded the Whig National Convention for the 1840 race. He initially supported General Winfield Scott, but really wanted to defeat Kentucky Senator Henry Clay, a slaveholder he felt could not carry New York state. Fillmore did not attend the convention, but was gratified when it nominated General william Henry Harrison for President, with former Virginia senator John Tyler his running mate. Fillmore organized Western New York for the Harrison campaign, and the national ticket was elected, while Fillmore easily gained a fourth term in the House.

At the urging of Senator Clay, Harrison quickly called a special session of Congress. With the Whigs to organize the House for the first time, Fillmore sought the Speakership, but it went to a Clay acolyte, John White of Kentucky. Nevertheless, Fillmore was made chairman of the House Ways and Means Committee. Harrison was expected to go along with anything Clay and other congressional Whig Leaders proposed, but died on April 4, 1841, elevating Vice President Tyler to the presidency. Tyler, a onetime maverick Democrat, soon broke with Clay over congressional proposals for a national bank to stabilize the currency, which he vetoed twice, leading to his expulsion from the Whig Party. Fillmore remained on the fringes of that conflict, generally supporting the congressional Whig position, but his chief achievement as Ways and Means chairman was the Tariff of 1842. The existing tariff did not protect Manufacturing, and part of the revenue was distributed to the states, a decision made in better times that was by then depleting the Treasury. Fillmore prepared a bill raising tariff rates that was popular in the country, but the continuation of distribution assured a Tyler veto, and much political advantage for the Whigs. Once Tyler vetoed it, a House committee headed by Massachusetts' John Quincy Adams condemned his actions. Fillmore prepared a second bill, this time omitting distribution, and when it reached his desk, Tyler signed it, but in the process offended his erstwhile Democratic allies. Thus, Fillmore not only achieved his legislative goal, but managed to politically isolate Tyler.

Weed had wanted the vice presidential nomination for Seward (who attracted few delegate votes), and Collier had acted to frustrate them in more ways than one, for with the New Yorker Fillmore as vice President, under the political customs of the time, no one from that state could be named to the cabinet. Fillmore was accused of complicity in Collier's actions, but this was never substantiated. Nevertheless, there were sound reasons for the selection of Fillmore, as he was a proven vote-getter from electorally crucial New York, and his track record in Congress and as a candidate showed his devotion to Whig doctrine, allaying fears he might be another Tyler were something to happen to General Taylor. Delegates remembered him for his role in the Tariff of 1842, and he had been mentioned as a vice presidential possibility along with Lawrence and Ohio's Thomas Ewing. His rivalry with Seward (already known for anti-slavery views and statements) made him more acceptable in the South.

The Democrats nominated Senator Silas Wright as their gubernatorial candidate, and former Tennessee governor James K. Polk for President. Although Fillmore worked to gain support among German-Americans, a major constituency, he was hurt among immigrants by the fact that New York City Whigs had supported a nativist candidate in the mayoral election earlier in 1844—Fillmore and his party were tarred with that brush. He was not friendly to immigrants, and blamed his defeat on "foreign Catholics". Clay was beaten as well. Fillmore's biographer Paul Finkelman suggested that the hostility to immigrants and weak position on slavery defeated him for governor.

President Polk had pledged not to seek a second term, and with gains in Congress during the 1846 election cycle, the Whigs were hopeful of taking the White House in 1848. The party's perennial candidates, Henry Clay and Daniel Webster, each wanted the nomination, and amassed support from congressional colleagues. Many rank and file Whigs backed the Mexican War hero, General Zachary Taylor, for President. Although Taylor was extremely popular, many northerners had qualms about electing a Louisiana slaveholder at a time of sectional tension over whether slavery should be allowed in the territories ceded by Mexico. Taylor's uncertain political views gave others pause—career Army, he had never cast a ballot for President, though he stated that he was a Whig supporter, and some feared they might elect another Tyler, or another Harrison.

It was customary in mid-19th century America for a candidate for high office not to appear to seek it. Thus, Fillmore remained at the comptroller's office in Albany, and made no speeches; the 1848 campaign was conducted in the newspapers and with addresses made by surrogates at rallies. The Democrats nominated Michigan Senator Lewis Cass for President, with General william O. Butler his running mate, but it would be a three-way fight as the Free Soil Party, opposed to the spread of slavery, chose former President Van Buren. There was a crisis among the Whigs when Taylor also accepted the presidential nomination of a group of dissident South Carolina Democrats. Fearing that Taylor would be an party apostate like Tyler, Weed in late August scheduled a rally in Albany aimed at electing an uncommitted slate of presidential electors, but Fillmore interceded with the Editor, assuring him that Taylor was loyal to the party.

Fillmore fought back against Weed by building a network of like-minded Whigs in New York state, with their positions publicized by the establishment of a rival newspaper to Weed's Albany Evening Journal. This was backed by wealthy New Yorkers. All pretense at friendship between Fillmore and Weed vanished in November 1849 when the two happened to meet in New York City, and they exchanged accusations.

Benson Lee Grayson suggested that the Fillmore administration's ability to avoid potential problems is too often overlooked. Fillmore's constant attention to Mexico avoided a resumption of the war and laid the groundwork for the Gadsden Treaty during Pierce's presidency. Meanwhile, the Fillmore administration resolved a controversy with Portugal left over from the Taylor administration, smoothed over a disagreement with Peru over guano islands, and peacefully resolved disputes with Britain, France, and Spain over Cuba. All of these crises were resolved without the United States going to war or losing face. Grayson also applauded Fillmore's firm stand against Texas' ambitions in New Mexico during the 1850 crisis. Fred I. Greenstein and Dale Anderson praised Fillmore for his resoluteness in his early months in office, noting that Fillmore "is typically described as stolid, bland, and conventional, but such terms underestimate the forcefulness evinced by his handling of the Texas–New Mexico border crisis, his decision to replace Taylor's entire cabinet, and his effectiveness in advancing the Compromise of 1850".

A much-publicized event of Fillmore's presidency was the arrival in late 1851 of Lajos Kossuth, the exiled leader of a failed Hungarian revolution against Austria. Kossuth wanted the U.S. to recognize Hungary's independence. Many Americans were sympathetic to the Hungarian rebels, especially recent German immigrants, who were now coming to the U.S. in large numbers and had become a major political force. Kossuth was feted by Congress, and Fillmore allowed a White House meeting after receiving word that Kossuth would not try to politicize it. In spite of his promise, Kossuth made a speech promoting his cause. The American enthusiasm for Kossuth petered out, and he departed for Europe; Fillmore refused to change American policy, remaining neutral.

As the election of 1852 approached, Fillmore remained undecided whether to run for a full term as President. Secretary Webster had long coveted the presidency and, though past seventy, planned a final attempt to gain the White House. Fillmore was sympathetic to the ambitions of his longtime friend, but though he issued a letter in late 1851 stating that he did not seek a full term, was reluctant to rule it out, fearing the party would be captured by the Sewardites. Thus, approaching the national convention in Baltimore, to be held in June 1852, the major candidates were Fillmore, Webster and General Scott. Weed and Seward backed Scott; in late May, the Democrats nominated former New Hampshire senator Franklin Pierce, who had been out of national politics for nearly a decade before 1852, but whose profile had risen as a result of his military Service in the Mexican War. The nomination of Pierce, a northerner sympathetic to the southern view on slavery, united the Democrats and meant the Whig candidate would face an uphill battle to gain the presidency.

Fillmore was the first President to return to private life without being independently wealthy or in possession of a landed estate, and, with no pension to anticipate, was unsure how he would make a living consistent with the dignity of his former office. His friend, Judge Hall, assured him that it would be proper for him to practice law in the higher courts of New York, and Fillmore intended to do so. The Fillmores had planned a tour of the South after leaving the White House, but Abigail caught a cold at President Pierce's inauguration, developed pneumonia, and died in Washington on March 30, 1853. A saddened Fillmore returned to Buffalo for the burial. The fact that he was in mourning limited his social activities, and he made ends meet on the income from his Investments. He was bereaved again on July 26, 1854 when his only daughter Mary died of cholera.

The former President ended his seclusion in early 1854, as debate over Senator Douglas's Kansas-Nebraska Bill embroiled the nation. This would open the northern portion of the Louisiana Purchase to settlement, including slavery, and would end the northern limit on slavery under the Missouri Compromise of 1820. Fillmore decided on an ostensibly nonpolitical national tour, hoping to rally disaffected Whig politicians to preserve the Union and back a run for President, for he retained many supporters. This occupied much of the late winter and spring of 1854. Fillmore made public appearances opening railroads and visiting the grave of Senator Clay, but met behind the scenes with politicians.

Later that year, Fillmore went abroad, stating publicly that as he lacked office, he might as well travel. The trip was at the advice of political friends, who felt that by touring, he would avoid involvement in the contentious issues of the day, and he spent over a year, from March 1855 to June 1856, in Europe and the Middle East. Queen Victoria is said to have pronounced the ex-president the handsomest man she had ever seen, while his presence in the gallery of the House of Commons at the same time as Van Buren excited a comment from MP John Bright. Fillmore was offered an honorary Doctor of Civil Law (D.C.L.) degree by the University of Oxford. Fillmore turned down the honor, explaining that he had neither the "literary nor scientific attainment" to justify the degree. He is also quoted as having explained that he "lacked the benefit of a classical education" and could not, therefore, understand the Latin text of the diploma, adding that he believed "no man should accept a degree he cannot read." Another possibility is that Fillmore refused the degree to escape the heckling and taunting to which Oxford students typically subjected the recipients of such honors.

Once Fillmore was back home in Buffalo, he had no excuse to make speeches, and his campaign stagnated through the summer and fall of 1856. Political fixers who had been Whigs, such as Weed, tended to join the Republican Party, and the Know Nothings lacked experience at selling anything but nativism. Accordingly, Fillmore's pro-Union stance mostly went unheard. Although the South was friendly towards Fillmore, many there feared a Frémont victory would lead to secession, and some sympathetic to Fillmore moved into the Buchanan camp lest the anti-Frémont vote be split, which might elect the Republican. Scarry suggested that the events of 1856, including the conflict in Kansas Territory and the caning of Charles Sumner on the floor of the Senate polarized the nation, making Fillmore's moderate stance obsolete.

With his defeat in 1856, Fillmore deemed his political career at an end. He again felt inhibited from returning to the practice of law. But his financial worries were removed when on February 10, 1858, Fillmore married Caroline McIntosh, a well-to-do widow. Their combined wealth allowed them to purchase a large house on Niagara Square in Buffalo, where they lived for the remainder of Millard Fillmore's life. There, the Fillmores devoted themselves to entertaining and philanthropy, according to Smith, "they generously supported almost every conceivable cause". Among these was the Buffalo Historical Society and the Buffalo General Hospital, which he helped found.

In the election of 1860, Fillmore voted for Senator Douglas, the nominee of the northern Democrats. After the vote, in which the Republican candidate, former Illinois representative Abraham Lincoln was elected, many sought out Fillmore's views but he refused to take any part in the secession crisis that followed, feeling that he lacked influence. He decried Buchanan's inaction as states left the Union, writing that while the federal government could not coerce a state, those advocating secession should simply be regarded as traitors. When Lincoln came to Buffalo en route to his inauguration, Fillmore led the committee selected to receive the president-elect, hosted him at his mansion, and took him to church. Once war came, Fillmore supported Lincoln in his efforts to preserve the Union. He commanded the Union Continentals, a corps of home guards of males over the age of 45 from the upstate New York area. The Continentals trained to defend the Buffalo area in the event of a Confederate attack. They performed military drill and ceremonial functions at parades, funerals, and other events. The Union Continentals guarded Lincoln's funeral train in Buffalo. They continued operations after the war, and Fillmore remained active with them almost until his death.

Despite Fillmore's zeal in the war effort, he was attacked in many newspapers when he gave a speech in early 1864 calling for magnanimity towards the South at war's end, and counting the heavy cost, financial and in blood, of the war. The Lincoln administration saw this as an attack on it, that could not be tolerated in an election year, and Fillmore was called a Copperhead and even a traitor. This led to lasting ill-feeling against Fillmore in many circles. In the 1864 presidential election Fillmore supported Democratic candidate George B. McClellan for the presidency, believing that the Democratic Party's plan for immediate cessation of fighting and allowing the seceded states to return with slavery intact was the best possibility for restoring the Union.

After Lincoln's assassination in April 1865, black ink was thrown on Fillmore's house as it was not draped in mourning like others, though he was apparently out of town at the time and put black drapes in the windows once he returned. Although he retained his position as Buffalo's leading citizen and was among those selected to escort the body when Lincoln's funeral train passed through Buffalo, there was still anger against him for his wartime positions. Fillmore supported President Andrew Johnson's Reconstruction policies, feeling that the nation needed to be reconciled as quickly as possible. Most of his time was devoted to his civic activities. He aided Buffalo in becoming the third American city, after Boston and Philadelphia, to have a permanent art gallery with the Buffalo Fine Arts Academy.

Fillmore stayed in good health almost to the end, but suffered a stroke in February 1874, and died after a second one on March 8. Two days later, he was buried at Forest Lawn Cemetery in Buffalo after a funeral procession of hundreds of notables; the U.S. Senate sent three of its members to honor its former President, including Lincoln's first vice President, Maine's Hannibal Hamlin.

Millard Fillmore, with his wife Abigail, established the first White House library. There are a number of remembrances of Millard Fillmore; his East Aurora house still stands, and sites honor him at his birthplace (where a replica log cabin was dedicated in 1963 by the Millard Fillmore Memorial Association) and boyhood home. A statue of Fillmore stands outside Buffalo City Hall. At the university he helped found, now SUNY Buffalo, Millard Fillmore Academic Center and Millard Fillmore College bear his name. On February 18, 2010, the United States Mint released the thirteenth coin in the Presidential $1 Coin Program, bearing Fillmore's likeness.

Although Fillmore has become something of a cult figure as America's most forgettable chief executive, Smith found him to be "a conscientious president" who chose to honor his oath of office and enforce the Fugitive Slave Act, rather than govern based on his personal preferences. Paul G. Calabresi and Christopher S. Yoo, in their study of presidential power, deemed Fillmore "a faithful executor of the laws of the United States—for good and for ill". But, according to Smith, the enforcement of the act has given Fillmore an undeserved pro-southern reputation. Fillmore's place in history has also suffered because "even those who give him high marks for his support of the compromise have done so almost grudgingly, probably because of his Know-Nothing candidacy in 1856". Smith argued that Fillmore's association with the Know Nothings looks far worse in retrospect than it did at the time, and that the former President was not motivated by nativism in his candidacy.

Fillmore was by then unpopular with northern Whigs for signing and enforcing the Fugitive Slave Act, but had considerable support from the South, where he was seen as the only candidate capable of uniting the party. Once the convention passed a party platform endorsing the Compromise as a final settlement of the slavery question, Fillmore was willing to withdraw, but found that many of his supporters could not accept Webster and his action would nominate Scott. The convention deadlocked, and this persisted through Saturday, June 19, when a total of 46 ballots had been taken; delegates adjourned until Monday. Party Leaders proposed a deal to both Fillmore and Webster: if the secretary could increase his vote total over the next several ballots, enough Fillmore supporters would go along to put him over the top; if he could not, Webster would withdraw in favor of Fillmore. The President quickly agreed, but Webster did not do so until Monday morning. On the 48th ballot, Webster delegates began to defect to Scott, and the general gained the nomination on the 53rd ballot. Webster was far more unhappy at the outcome than was Fillmore, who refused the secretary's resignation. Bereft of the votes of much of the South, and also of Northerners who depended on peaceful intersectional trade, Scott was easily beaten by Pierce in November. Smith suggested that the Whigs might have done much better with Fillmore.