After traveling and studying around Europe, Preston studied law at the University of Edinburgh in Scotland. He sailed back to the States in 1819 and was admitted to the bar of Virginia in 1820. He practiced law there for two years. He then moved to Columbia, South Carolina in 1822 and ran unsuccessfully for election to the Twenty-Second Congress. He was, however, elected to the South Carolina House of Representatives and served from 1828 to 1834. He was then elected in 1833 as a Nullifier to the United States Senate to fill the vacancy after the resignation of Stephen D. Miller. During his first year in the Senate, his oratorical gifts led the Whig leadership to give him a prominent role in the effort to censure Andrew Jackson, elevating Preston "far in advance of most of his colleagues, and side by side with Clay, Webster, Calhoun, and Clayton."[3] Preston was then reelected as a Whig in 1837 and served until his resignation on November 29, 1842. During that time he served as the chairman for the Committee on the Library and the Committee on Military Affairs. Preston was the only Whig to serve as a senator from South Carolina.
After his resignation, Preston returned to practicing law and served as president of South Carolina College from 1845 until 1851, when he resigned due to poor health. He died in Columbia, South Carolina. He was buried in the Trinity Episcopal Churchyard.
He is the namesake of Lake Preston, in South Dakota.[4] Preston College at the University of South Carolina is named in his honor; in July 2021, the university's Presidential Commission on University History recommended renaming the college.[1]
