After his father's death in 1817, his mother remarried and removed to Troy, New York. Yancey attended Williams College for one year, studied law at Greenville, South Carolina, and was admitted to the bar. As editor of the Greenville (South Carolina) Mountaineer (1834-35), he ardently opposed nullification.

In 1835 he married a wealthy woman, and in the winter of 1836-1837 removed to her plantation in Alabama, near Cahaba (Dallas County), and edited weekly papers there and in Wetumpka (Elmore County), his summer home. The accidental poisoning of his slaves in 1839 forced him to devote himself entirely to law and journalism; he was now an impassioned advocate of States' Rights and supported Van Buren in the presidential campaign of 1840.

He was elected in 1841 to the Alabama House of Representatives, in which he served for one year; he became a state senator in 1843, and in 1844 was elected to the United States House of Representatives to fill a vacancy, being re-elected in 1845. In Congress his ability and his unusual oratorical gifts at once gained recognition. In 1846, however, he resigned his seat, partly on account of poverty, and partly because of his disgust with the Northern Democrats, whom he accused of sacrificing their principles to their economic interests.

His entire energy was now devoted to the task of exciting resistance to anti-slavery aggression. He is generally included as one of several southerners referred to as "fire-eaters". In 1848 he secured the adoption by the state Democratic convention of the so-called "Alabama Platform," which was endorsed by the legislatures of Alabama and Georgia and by Democratic state conventions in Florida and Virginia, declaring that it was the duty of Congress not enly to allow slavery in all the territories but to protect it, that a territorial legislature could not exclude it, and that the Democratic party should not support for president or vice-president a candidate "not ... openly and unequivocally opposed to either of the forms of excluding slavery from the territories of the United States mentioned in these resolutions."

When the conservative majority in the national Democratic convention in Baltimore refused to incorporate his ideas into the platform, Yancey with one colleague left the convention and wrote an Address to the People of Alabama, defending his course and denouncing the cowardice of his associates. Naturally, he opposed the Compromise of 1850, and went so far as openly to advocate secession; but the conservative element was in control of the state.

Disappointment of the South with the results of "Squatter Sovereignty" caused a reaction in his favour, and in 1858 he wrote a letter advocating the appointment of committees of safety, the formation of a League of United Southerners, and the repeal of the laws making the African slave-trade piracy. After twelve years' absence from the national conventions of the Democratic party, he attended the Charleston convention hv April 1860, and again demanded the adoption of his ideas. Defeated by a small majority, he again left the hall, followed this time by the delegates of Alabama, Mississippi, Louisiana, South Carolina, Florida, Texas, and two of the three delegates from Delaware.

On the next day the Georgia delegation and a majority of the Arkansas delegation withdrew. In the Baltimore convention of the seceders he advocated the nomination of John Cabell Breckinridge, and he made a tour of the country on his behalf. In Alabama he was the guiding spirit in the secession convention and delivered the address of welcome to Jefferson Davis on his arrival at Montgomery. He refused a place in President Davis's cabinet. On March 31, 1861 he sailed for Europe as the head of a commission sent to secure recognition of the Confederate government, but returned in 1862 to take a seat in the Confederate Senate, in which he advocated a more vigorous prosecution of the war. On account of his failing health, he left Richmond early in 1863, and on the 27th of July died at his home near Montgomery.

Yancey's nephew, Joseph H. Earle, was a U.S. Senator from South Carolina.