Smith was elected to the Twentieth Congress (March 4, 1827–March 3, 1829) and was an unsuccessful candidate for reelection in 1828; he was then elected as a Whig to the U.S. Senate and served from March 4, 1837, to March 3, 1843. While in the Senate, he was chairman of the Committee on Engrossed Bills (Twenty-sixth Congress) and a member of the Committee on Public Lands (Twenty-seventh Congress). He was an unsuccessful candidate for reelection and moved to Indianapolis where he resumed the practice of law. He declined to be a candidate for Governor of Indiana in 1845 and engaged in the railroad business in Indianapolis. He died in that city in 1859; interment was in Crown Hill Cemetery.