King was born in Sampson County, North Carolina, and graduated from the University of North Carolina in 1803. He was admitted to the bar in 1806 and began practice in Clinton, North Carolina. He was a member of the State House of Commons from 1807 to 1809, city solicitor of Wilmington, North Carolina in 1810, and elected to the Twelfth, Thirteenth, and Fourteenth Congresses, serving from March 4, 1811 until November 4 1816, when he resigned. King was secretary of the legation at Naples and later at Saint Petersburg. He returned to the United States in 1818 and located in Cahaba, Alabama, where he became a planter.
King was a delegate to the convention which organized the State government. Upon the admission of Alabama as a State in 1819 he was elected as a Democratic-Republican to the United States Senate, and was reelected as a Jacksonian in 1822, 1828, 1834, and 1841, serving from December 14, 1819, until April 15, 1844, when he resigned. He served as President pro tempore of the United States Senate during the Twenty-fourth through Twenty-seventh Congresses. King was Chairman of the Committee on Public Lands and the Committee on Commerce.
He was Minister to France from 1844 to 1846. He was appointed and subsequently elected as a Democrat to the Senate to fill the vacancy caused by the resignation of Arthur P. Bagby and served from July 1, 1848 until his resignation on December 20, 1852 due to poor health. He served as President pro tempore of the Senate during the Thirty-first and Thirty-second Congresses and was Chairman of the Committee on Foreign Relations and Committee on Pensions. He was elected Vice President of the United States on the Democratic ticket with Franklin Pierce in 1852 and took the oath of office March 4, 1853, in Havana, Cuba, where he had gone for his health, which was a privilege extended by special act of Congress. In honor of his inauguration, the newly formed Washington Territory created a county named for him. (King County still exists, but was rechristened in 1986 to honor civil rights leader Dr. Martin Luther King, Jr.)
Some historians have speculated that King may have been gay, and that he had a long-term intimate relationship with James Buchanan. The theory is controversial and a source of debate among Buchanan and King historians.