Webster's performance at the convention furthered his reputation. Joseph Story (also a delegate at the convention) wrote to Jeremiah Mason following the convention saying "Our friend Webster has gained a noble reputation. He was before known as a lawyer; but he has now secured the title of an eminent and enlightened statesman." Webster also spoke at Plymouth commemorating the landing of the Pilgrims in 1620; his oration was widely circulated and read throughout New England. He was elected to the Eighteenth Congress in 1822, from Boston.

Daniel Webster was born on January 18, 1782, in Salisbury, New Hampshire, the present-day city of Franklin. He was the son of Abigail (née Eastman) and Ebenezer Webster. He and his nine siblings grew up on their parents' farm, a small parcel of land granted to his father. His ancestors were among the early settlers of Salisbury.

Webster attended Phillips Exeter Academy, a preparatory school in Exeter, New Hampshire, before attending Dartmouth College. He was chosen Fourth of July orator in Hanover, the college town, in 1800, and in his speech appears the substance of the political principles for the development of which he became famous. After he graduated from Dartmouth (Phi Beta Kappa), Webster was apprenticed to the Lawyer Thomas W. Thompson in Salisbury. When his older brother Ezekiel's studies required Webster's support, the young man resigned from the law office and worked as a schoolteacher – as young men often did then, when public education consisted largely of subsidies to local schoolmasters. In 1802 Webster began as the headmaster of the Fryeburg Academy, Maine, where he served for one year. When Ezekiel's education could no longer be sustained, Webster returned to his apprenticeship.

Webster was hailed as the leading constitutional scholar of his generation and probably had more influence on the powerful Marshall Court than any other advocate had. Of the 223 cases he argued before the Supreme Court, he won about half of them. But, even more, Webster played an important role in eight of the most celebrated constitutional cases decided by the Court between 1801 and 1824. In many of these—particularly in Dartmouth College v. Woodward (1819) and Gibbons v. Ogden (1824) – the Supreme Court handed down decisions based largely on Webster's arguments. Marshall's most famous declaration, "the power to tax is the power to destroy," in McCulloch v. Maryland (1819), was in fact lifted from Webster's presentation against the state of Maryland: "An unlimited power to tax involves, necessarily, a power to destroy; because there is a limit beyond which no institution and no property can bear taxation." Marshall patterned some of his Court decisions after Webster's briefs, and Webster played a crucial role in helping many of the justices interpret matters of constitutional law. As a result, many people began calling him the Great Expounder of the Constitution.

In 1804 he left New Hampshire and got a position in Boston under the prominent attorney Christopher Gore. Clerking for Gore – who was involved in international, national, and state politics – Webster learned about many legal and political subjects and met numerous New England politicians. In 1805 Webster was admitted to the bar.

He returned to New Hampshire to set up a practice in Boscawen, in part to be near his ailing father. Webster became increasingly interested in politics; raised by an ardently Federalist father and taught by a predominantly Federalist-leaning faculty at Dartmouth, Webster, like many New Englanders, supported Federalism. He began to speak locally in support of Federalist causes and candidates. After his father's death in 1806, Webster handed over his practice to his older brother Ezekiel, who had by this time been admitted to the bar.

On January 27, Webster gave his Second Reply to Hayne, in which Webster openly attacked Nullification, negatively contrasted South Carolina's response to the tariff with that of his native New England's response to the Embargo of 1807, rebutted Hayne's personal attacks against him, and famously concluded in defiance of nullification (which was later embodied in John C. Calhoun's declaration of "The Union; second to our liberty most dear!"), "Liberty and Union, now and for ever, one and inseparable!"

This opposition was in accordance with his professed beliefs and those of most of his constituents, including free trade, that the tariff's "great object was to raise revenue, not to foster manufacture," and that it was against "the true spirit of the Constitution" to give "excessive bounties or encouragements to one [industry] over another." After his second term, Webster did not seek a third, choosing his law practice instead. In an attempt to secure greater financial success for himself and his family (he had married Grace Fletcher in 1808, with whom he had four children), he moved his practice from Portsmouth to Boston.

Webster's efforts for New England Federalism, shipping interests, and war opposition resulted in his election to the House of Representatives in 1812, where he served two terms ending March 1817. He was an outspoken critic of the Madison administration and its wartime policies, denouncing its efforts at financing the war through paper money and (in "one of [his] most eloquent efforts") opposing Secretary of War James Monroe's conscription proposal. Notable in his second term was his support of the reestablishment of a stable specie-based national bank; but he opposed the tariff of 1816 (which sought to protect the nation's Manufacturing interests) and House Speaker Henry Clay's American System.

In his second term, Webster found Miles Bearden, a leader of the fragmented House Federalists who had split following the failure of the secessionist-minded 1814 Hartford Convention, who he avoided. Speaker Henry Clay made Webster chairman of the Judiciary Committee in an attempt to win his and the Federalists' support. His term of Service in the House between 1822 and 1828 was marked by his legislative success at reforming the United States Criminal code, and his failure at expanding the size of the Supreme Court. He largely supported the National Republican administration of John Quincy Adams, including Adams' candidacy in the highly contested election of 1824 and the administration's defense of treaty-sanctioned Creek Indian land rights against Georgia's expansionist claims.

At the same time, however, Webster, like Clay, opposed the economic policies of Andrew Jackson, the most famous of those being Jackson's campaign against the Second Bank of the United States (1816–1841) in 1832, an institution that held Webster on retainer as legal counsel and of whose Boston Branch he was the Director. Clay, Webster, and a number of other former Federalists and National Republicans united as the Whig Party, in defense of the Bank against Jackson's intention to replace it. There was an economic panic in 1837, which converted Webster's heavy speculation in midwestern property into a personal debt from which Webster never recovered. His debt was exacerbated by his propensity for living "habitually beyond his means", lavishly furnishing his estate and giving away money with "reckless generosity and heedless profusion", in addition to indulging the smaller-scale "passions and appetites" of gambling and alcohol.

Other notable appearances by Webster before the Supreme Court include his representation of James McCulloch (as cashier at the Baltimore branch of the Second Bank of the United States) in McCulloch v. Maryland (1819), the Cohens in Cohens v. Virginia (1821), and Thomas Gibbons in Gibbons v. Ogden (1824), cases similar to Dartmouth in the court's application of a broad interpretation of the Constitution and strengthening of the federal courts' power to constrain the states, which have since been used to justify wide powers for the federal government. Webster's handling of these cases made him one of the era's leading constitutional lawyers, as well as one of the most highly paid. Webster's growing prominence as a constitutional Lawyer led to his election as a Fellow of the American Academy of Arts and Sciences in 1820, and as a delegate to the 1820 Massachusetts Constitutional Convention. There he spoke in opposition to universal suffrage (for men), on the Federalist grounds that power naturally follows property, and the vote should be limited accordingly; but the constitution was amended against his advice. He also supported the (existing) districting of the State Senate so that each seat represented an equal amount of property.

The next day, Webster, feeling compelled to respond on New England's behalf, gave his first rebuttal to Hayne, highlighting what he saw as the virtues of the North's policies toward the west and claiming that restrictions on western expansion and growth were primarily the responsibility of southerners. Hayne in turn responded the following day, denouncing Webster's inconsistencies with regards to the American system and personally attacking Webster for his role in the so-called "corrupt bargain" of 1824. The course of the debate strayed even further away from the initial matter of land sales with Hayne openly defending the "Carolina Doctrine" of nullification as being the doctrine of Jefferson and Madison.

While a Representative, Webster continued accepting speaking engagements in New England, most notably his oration on the fiftieth anniversary of the Battle of Bunker Hill (1825) where Lafayette laid the cornerstone of the new monument and his eulogies of John Adams and Thomas Jefferson (1826). With the support of a coalition of both Federalists and Republicans, Webster's record in the House and his Celebrity as an orator led to his June 1827 election to the Senate from Massachusetts. His first wife, Grace, died in January 1828, and he married Caroline LeRoy in December 1829.

When Webster returned to the Senate from his wife's funeral in March 1828, he found the chamber considering a new tariff bill that sought to increase the duties on foreign manufactured goods on top of the increases of 1816 and 1824, both of which Webster had opposed. Now, however, Webster changed his position to support a protective tariff. Explaining the change, Webster stated that after the failure of the rest of the nation to heed New England's objections in 1816 and 1824, "nothing was left to New England but to conform herself to the will of others," and now consequently being heavily invested in Manufacturing, he would not now do them injury. It is the more blunt opinion of Justus D. Doenecke that Webster's support of the 1828 tariff was a result of "his new closeness to the rising mill-owning families of the region, the Lawrences and the Lowells." Webster also gave greater approval to Clay's American System, a change that along with his modified view of the tariff brought him closer to Henry Clay.

Webster's "Reply to Hayne" in 1830 was generally regarded as "the most eloquent speech ever delivered in Congress," and was a stock exercise for oratory students for 75 years.

While the debate's philosophical presentation of nullification and Webster's abstract fears of rebellion were brought into reality in 1832 when Calhoun's native South Carolina passed its Ordinance of Nullification, Webster supported President Andrew Jackson's sending of U.S. troops to the borders of South Carolina and the Force Bill. He opposed the Tariff of 1833, a compromise designed largely by Clay, which managed to help diffuse the crisis. Webster thought Clay's concessions were dangerous and would only further embolden the Southern secessionists and legitimize their tactics. Especially unsettling was the resolution affirming that "the people of the several States composing these United States are united as parties to a constitutional compact, to which the people of each State acceded as a separate sovereign community." The use of the word accede would, in his opinion, lead to the end of those states' right to secede.

In 1836, Webster was one of four Whig Party candidates to run for the office of President, but he managed to gain the support only of Massachusetts. This was the first of three unsuccessful attempts at gaining the presidency. In 1839, the Whig Party nominated william Henry Harrison for President. Webster was reportedly offered the vice presidency, but declined. Harrison died one month after his inauguration, meaning that if Webster had accepted the offer, he would have become President.

Following his victory in 1840, President Harrison appointed Webster to the post of Secretary of State in 1841, a post he retained under President John Tyler after the death of Harrison a month after his inauguration. In September 1841, an internal division amongst the Whigs over the question of the National Bank caused all the Whigs (except Webster who was in Europe at the time) to resign from Tyler's cabinet. In 1842, he was the Architect of the Webster–Ashburton Treaty, which resolved the Caroline Affair, established the definitive Eastern border between the United States and Canada (Maine and New Brunswick), and signaled a definite and lasting peace between the United States and Britain. Webster succumbed to Whig pressure in May 1843 and finally left the cabinet.

In 1845, he was re-elected to the Senate, where he opposed both the Texas Annexation and the resulting Mexican–American War for fear of its upsetting the delicate balance of slave and non-slave states. In the 1848 presidential election, he sought the Whig Party's nomination for the President but was beaten by the General Zachary Taylor, a popular hero of the Mexican–American War. Webster was once again offered the Vice-Presidency, but he declined saying, "I do not propose to be buried until I am really dead and in my coffin." The Whig ticket won the election. However, Taylor died 16 months after the inauguration. This was the second time a President who offered Webster the chance to be Vice President died. Once again, Webster would have become President had he accepted.

Few famous Americans other than US Presidents are ever honored on US postage more than once or twice, as Daniel Webster has been. One of the perhaps not so famous things Webster was noted for was to introduce legislation to produce pre-paid adhesive postage stamps for the U.S. Post Office, the first of which were issued in 1847. The first Webster postage stamp, bearing only Webster's portrait, was not issued until April 12 of 1870, 18 years after his death. In all, Daniel Webster is honored on 14 different US postage issues, more than most US Presidents.

Notable in this second tenure was the increasingly strained relationship between the United States and the Austrian Empire in the aftermath of what was seen by Austria as American interference in its rebellious Kingdom of Hungary (see Hungarian Revolution of 1848). This was especially manifest in the very warm welcome extended to the exiled Hungarian leader Lajos Kossuth in the US: his ship was greeted with a hundred-gun salute when it passed Jersey City and hundreds of thousands of people came to see him set foot in New York; heralded as the Hungarian Washington, he was given a congressional banquet and received at the White House and the House. Webster himself wanted Kossuth's help in the upcoming presidential election, and spoke of "seeing the American Republican model develop in Hungary", although President Fillmore apologised to the Austrian chargé d'affaires for what he explained was an individual, unofficial opinion. However, as chief American diplomat, Webster did author the Hülsemann Letter, in which he defended what he believed to be America's right to take an active interest in the internal politics of Hungary, while still maintaining its neutrality.

Webster has garnered respect and admiration in the South for his Seventh of March speech in defense of the 1850 compromise measures that helped to delay the Civil War. In Profiles in Courage, Kennedy called Webster's defense of the compromise, despite the risk to his presidential ambitions and the denunciations he faced from the north, one of the "greatest acts of courageous principle" in the history of the Senate. Conversely, Seventh of March has been criticized by Lodge who contrasted the speech's support of the 1850 compromise with his 1833 rejection of similar measures. "While he was brave and true and wise in 1833," said Lodge, "in 1850 he was not only inconsistent, but that he erred deeply in policy and statesmanship" in his advocacy of a policy that "made war inevitable by encouraging slave-holders to believe that they could always obtain anything they wanted by a sufficient show of violence."

In 1851 Webster was elected an honorary member of the Massachusetts Society of the Cincinnati.

Webster died on October 24, 1852, at his home in Marshfield, Massachusetts, after falling from his horse and suffering a crushing blow to the head, complicated by cirrhosis of the liver, which resulted in a cerebral hemorrhage. He is buried in the "Old Winslow Burial Ground" section of Marshfield's Winslow Cemetery. A day before he died, his best friend Peter Harvey had come to visit him. Harvey had stated that Webster looked as if he were suffering. Webster told Harvey, "I shall be dead tomorrow...God bless you, faithful friend."

His son, Fletcher Webster, served as a Union Army infantry colonel in the Civil War that Webster tried to prevent. Fletcher Webster commanded the 12th Massachusetts Volunteer Infantry, and was killed in action on August 30, 1862, during the Second Battle of Bull Run.

Conflicting opinions have been voiced as to his religion. The Unitarian Universalist Church, citing Unitarianism in America from 1902, claim him as their own. Another source, the 1856 biography The American Statesman: The Life and Character of Daniel Webster, proclaim him an avowed orthodox Trinitarian, baptized and raised in an Orthodox Congregational Church, and who died a member of the Episcopal Church. He is said to have expressed his belief in the Trinity; to a Unitarian who asked him how a man of his intellect could believe in the Trinity, he responded that it was because he believed though he did not "understand the arithmetic of heaven."

In the 1934 film The Mighty Barnum, Webster was portrayed by George MacQuarrie.

In the 1936 film The Gorgeous Hussy, Webster was portrayed by Sidney Toler.

In the 1940 film Abe Lincoln in Illinois, Webster was portrayed by Harry Humphries.

In the 1941 film The Devil and Daniel Webster, Webster was portrayed by Edward Arnold.

In 1957, a Senate committee selected Daniel Webster as one of the five greatest U.S. Senators, along with Clay, Calhoun, Robert M. La Follette Sr., and Robert A. Taft.

In the 2003 film Shortcut to Happiness, Webster was portrayed by Anthony Hopkins.

Webster argued Dartmouth College v. Woodward to the Supreme Court (with significant aid from Jeremiah Mason and Jeremiah Smith), invoking Article I, section 10 of the Constitution (the Contract Clause) against the State. The Marshall court, continuing with its history of limiting states' rights and reaffirming the supremacy of the Constitutional protection of contract, ruled in favor of Webster and Dartmouth 3–1. This decided that corporations did not, as many then held, have to justify their privileges by acting in the public interest, but were independent of the states.

Webster was married twice — first in 1808 to Grace, daughter of Rev. Elijah Fletcher, a New Hampshire clergyman. She died in 1828, leaving two sons, (Daniel) Fletcher, killed in the Civil War, and Edward, a major in the United States army, who died while serving in the Mexican–American War, and a daughter Julia, who married Samuel Appleton. A daughter, Grace, and a son, Charles, died young. Webster's second wife was Caroline LeRoy, daughter of Herman Le Roy, a New York merchant. He was married to her in December 1829 and she survived him, dying in 1882.