King was born in Sampson County, North Carolina, to william King and Margaret deVane. His family was large, wealthy and well-connected. He graduated from the University of North Carolina at Chapel Hill in 1803, where he was also a member of the Philanthropic Society. Admitted to the bar in 1806 after reading the law with Judge william Duffy of Fayetteville, North Carolina, he began practice in Clinton. King was an ardent Freemason, and was a member of Fayetteville's Phoenix Lodge No. 8.
King entered politics and was elected as a member of the North Carolina House of Commons, where he served from 1807 to 1809, and he became city solicitor of Wilmington, North Carolina in 1810. He was elected to the Twelfth, Thirteenth and Fourteenth Congresses, serving from March 4, 1811 until November 4, 1816, when he resigned to become Secretary of the Legation for william Pinkney during Pinkney's appointment as Minister to Russia and special diplomatic mission in Naples.
When he returned to the United States in 1818, King joined the westward migration of the cotton culture to the Deep South, purchasing property at what would later be known as "King's Bend" between present-day Selma and Cahaba on the Alabama River in Dallas County of the new Alabama Territory, which had been recently separated from Mississippi. He developed a large cotton plantation based on slave labor, calling the property "Chestnut Hill". King and his relatives formed one of the largest slaveholding families in the state, collectively owning as many as 500.
King was a follower of Andrew Jackson, and was reelected to the Senate as a Jacksonian in 1822, 1828, 1834, and 1841, serving from December 14, 1819, until his resignation on April 15, 1844. During this time, in March–April 1824, william R. King was honored with a single vote at the Democratic-Republican Party Caucus to be the party's candidate for the Office of U.S. Vice President for the upcoming 1824 Presidential election. Later he served as President pro tempore of the United States Senate during the 24th through 27th Congresses. King was Chairman of the Senate's Committee on Public Lands and the Committee on Commerce.
While many believe King may have been asexual or heterosexual (but celibate), and there are many indicators that suggest he was homosexual, there is evidence to support the fact that he in fact did have a heterosexual relationship and possibly children. In Washington City on December 8th, 1824 he wrote a personal letter to then Alabama Governor, Israel Pickens regarding his "wayward heart that loves but once and loved forever." Pickens wife had recently passed away. King wrote that "...unfortunate as you have been in the loss of a most amiable and excellent woman, I am almost induced to envy you when I contrast your situation with mine; her lovely offspring are with you, you are training them up in the paths of virtue, and they bid fair to be an ornament to their Country, and to make glad the heart of their Father in the evening of his days." King continued, "You ask, why should it be so? I can only say such is the decree of fate; mine is a wayward heart that loves but once and loved forever. Of Petersburg or of those residing in its vicinity, I know but little, between me and them there never was a community of sentiment, variety, and youthful folly, may have mislead me for a — moment, but returning reason convinced me that perfect esteem entwined my Desire ineffable." Was he speaking of Petersburg, Georgia now covered by a large TVA lake or Petersburg, Virginia outside of Washington. It is unclear but this is clear evidence of a lost love "...of Petersburg" and "...of those residing in this vicinity."
The source of this interest has been King's close and intimate relationship with President James Buchanan. The two men lived together for 13 years from 1840 until King's death in 1853. Buchanan referred to the relationship as a "communion", and the two attended all parties together. Contemporaries also noted the closeness. Andrew Jackson called them "Miss Nancy" and "Aunt Fancy" (the former being a 19th-century euphemism for an effeminate man), while Aaron V. Brown referred to King as Buchanan's "better half". James Loewen has described Buchanan and King as "siamese twins".
Buchanan adopted King's mannerisms and romanticised view of southern culture. Both had strong political ambitions and in 1844 they planned to run as President and vice President. Both men were soft, effeminate and eccentric. They spent some time apart while King was on overseas missions in France, and their letters remain cryptic, avoiding revealing any personal feelings at all. In May 1844, Buchanan wrote to Cornelia Roosevelt, "I am now 'solitary and alone,' having no companion in the house with me. I have gone a wooing to several gentlemen, but have not succeeded with any one of them. I feel that it is not good for man to be alone, and [I] should not be astonished to find myself married to some old maid who can nurse me when I am sick, provide good dinners for me when I am well, and not expect from me any very ardent or romantic affection."
He was appointed as Minister to France, and served from 1844 to 1846. After his return, King resumed serving in the Senate, appointed and subsequently elected to fill the vacancy caused by the resignation of Arthur P. Bagby. He held his seat from July 1, 1848 until resigning because of ill health on December 20, 1852, after having been elected Vice President.
On July 11, 1850, two days after the death of President Zachary Taylor, King was appointed Senate President pro tempore. Because Millard Fillmore ascended to the presidency, the vice presidency was vacant, making King first in the line of succession under the law then in effect. He also served as Chairman of the Senate's Committee on Foreign Relations and the Committee on Pensions.
Pierce and King defeated the Whig candidates, Winfield Scott and william Alexander Graham. (While attending college, King and Graham had been members of rival campus organizations in Chapel Hill; King belonging to the Philanthropic Society and Graham to the Dialectic Society.) Because King was ill with tuberculosis and had traveled to Cuba in an effort to regain his health, he was not able to be in Washington to take his oath of office on March 4, 1853. By a Special Act of Congress, he was allowed to take the oath outside the United States, and was sworn in on March 24, 1853 near Matanzas, Cuba.