George Mifflin Dallas was born on July 10, 1792, to Alexander James Dallas and Arabella Maria Smith Dallas (born Devon, England) in Philadelphia. His father, born in Kingston, Jamaica, and educated in Edinburgh, was the Secretary of the Treasury under United States President James Madison, and was also briefly the Secretary of War. George Dallas was given his middle name after Thomas Mifflin, another Politician who was good friends with his father.

Dallas was the second of six children, another of whom, Alexander, would become the commander of Pensacola Navy Yard. During Dallas's childhood, the family lived in a mansion on Fourth Street, with a second home in the countryside, situated on the Schuylkill River. He was educated privately at Quaker-run preparatory schools, before studying at the College of New Jersey (now Princeton University), from which he graduated with highest honors in 1810. While at College, he participated in several activities, including the American Whig–Cliosophic Society. Afterwards, he studied law, and was admitted to the Pennsylvania bar in 1813.

After the War of 1812 ended, Pennsylvania's political climate was chaotic, with two factions in that state's Democratic party vying for control. One, the Philadelphia-based "Family party", was led by Dallas, and it espoused the beliefs that the Constitution of the United States was supreme, that an energetic national government should exist that would implement protective tariffs, a powerful central banking system, and undertake internal improvements to the country in order to facilitate national commerce. The other faction was called the "Amalgamators", headed by the Future President James Buchanan.

The Family party gained control of the Philadelphia city councils, and in 1828 elected Dallas as mayor. Boredom with that post quickly led Dallas—in his father's path—to the position of district attorney for the eastern district of Pennsylvania, where he stayed from 1829 to 1831. In December 1831 he won a five-man, eleven-ballot contest in the state legislature for election to an unexpired term in the U.S. Senate. In the Senate for only fourteen months, he chaired the Naval Affairs Committee and supported President Andrew Jackson's views on protective tariffs and the use of force to enforce the federal tariff in South Carolina.

Voters elected Dallas Mayor of Philadelphia as the candidate of the Family party, after the party had gained control of the city councils. However, he quickly grew bored of that post, and became the United States attorney for the eastern district of Pennsylvania in 1829, a position his father had held from 1801 to 1814, and continued in that role until 1831. In December of that year, he won a five-man, eleven-ballot contest in the state legislature, that enabled him to become the Senator from Pennsylvania in order to complete the unexpired term of the previous senator who had resigned.

Dallas served less than fifteen months—from December 13, 1831, to March 3, 1833. He was chairman of the Committee on Naval Affairs. Dallas declined to seek re-election, in part due to a fight over the Second Bank of the United States, and in part because his wife did not want to leave Philadelphia for Washington.

The tension with Buchanan intensified in 1833–1834, when Buchanan returned from his diplomatic post in Russia and was elected to Pennsylvania's other seat in the U.S. Senate.

Although off the national stage, Dallas remained active in state Democratic politics. Dallas turned down opportunities to return to the Senate and to become U.S. Attorney General. Instead, he accepted an appointment as state Attorney General, holding that post until 1835, when control of the state party machinery shifted from the declining Family party to Buchanan's Amalgamators."

In 1837, it was Dallas' turn for political exile, as newly elected President Martin Van Buren named him U.S. minister to Russia. Although Dallas enjoyed the social responsibilities of that post, he soon grew frustrated at its lack of substantive duties and returned to the United States in 1839. He found that during his absence in St. Petersburg, Buchanan had achieved a commanding position in Pennsylvania politics.

In December 1839, Van Buren offered to appoint Dallas as U.S. Attorney General after Buchanan had rejected the post. Dallas again declined the offer and spent the following years building his Philadelphia law practice. His relations with Buchanan remained troubled throughout this period.

At the May 1844 Democratic National Convention in Baltimore, James K. Polk and Silas Wright were nominated as the Democratic ticket. However, when Wright declined the nomination, they chose Dallas as his replacement. Dallas, who was not at the convention, was woken up at his home by convention delegates who had traveled to Philadelphia to tell him the news. Dallas somewhat reluctantly accepted the nomination. The Democratic candidates won the popular vote by a margin of 1.5%, and won the election with an electoral vote of 170 out of 275.

He remained at odds with Buchanan for many years. In 1845, when Buchanan was appointed Secretary of State by President Polk, Dallas vehemently objected.

Despite Dallas' efforts to avoid taking a stand, the Senate completed its voting on the Walker Tariff with a 27-to-27 tie. (A twenty-eighth vote in favor was held in reserve by a Senator who opposed the measure but agreed to follow the instructions of his state legislature to support it.) When he cast the tie-breaking vote in favor of the tariff on July 28, 1846, Dallas rationalized that he had studied the distribution of Senate support and concluded that backing for the measure came from all regions of the country. Additionally, the measure had overwhelmingly passed the House of Representatives, a body closer to public sentiment. He apprehensively explained to the citizens of Pennsylvania that "an officer, elected by the suffrages of all twenty-eight states, and bound by his oath and every constitutional obligation, faithfully and fairly to represent, in the execution of his high trust, all the citizens of the Union" could not "narrow his great sphere and act with reference only to [Pennsylvania's] interests." While his action, based on a mixture of party loyalty and political opportunism, earned Dallas the respect of the President and certain party leaders—and possible votes in 1848 from the southern and western states that supported low tariffs—it effectively demolished his home state political base, ending any serious prospects for Future elective office. (He even advised his wife in a message hand-delivered by the Senate Sergeant at Arms, "If there be the slightest indication of a disposition to riot in the city of Philadelphia, owing to the passage of the Tariff Bill, pack up and bring the whole brood to Washington.")

In 1856, Franklin Pierce appointed Dallas minister to Great Britain, and continued in that post from February 4, 1856, until the appointment by President Lincoln of Charles F. Adams, who relieved him on May 16, 1861. At the very beginning of his diplomatic Service in England he was called to act upon the Central American question, and the request made by the United States to the British government that Sir John Crampton, the British minister to the United States, should be recalled. Mr. Dallas managed these delicate questions in a conciliatory spirit, but without any sacrifice of national dignity, and both were settled amicably. At the close of his diplomatic career Mr. Dallas returned to private life and took no further part in public affairs except to express condemnation of secession.

Dallas returned to Philadelphia, and lived in Philadelphia until his death from a heart attack on December 31, 1864, at the age of 72. He is interred in St. Peter's Churchyard.

Other U.S. cities and towns named in Dallas' honor include Dallas, Georgia (the county seat of Paulding County, Georgia), Dallas, North Carolina (the former county seat of Gaston County, North Carolina), Dallas, Oregon (the county seat of Polk County, Oregon) and Dallastown, Pennsylvania It is debated whether the city of Dallas, Texas is named after the Vice President—see History of Dallas, Texas (1839–1855) for more information.

Dallas was a political rival of fellow Pennsylvanian James Buchanan, the Future 15th President of the United States. The rivalry was rooted in the power struggle in the Pennsylvania Democratic Party between the "Family party" and the "Amalgamators".