Knight was elected in 1821 as a Democratic-Republican to the U.S. Senate to fill the vacancy caused by the death of James Burrill, Jr.; he was re-elected in 1823 as a Crawford Republican, in 1829 as an Anti-Jacksonian, and again in 1835 as a Whig, and served from January 9, 1821, to March 3, 1841. While in the Senate he was chairman of the Committee to Audit and Control the Contingent Expenses (Twenty-second, Twenty-third and Twenty-sixth Congresses) and a member of the Committee on Manufactures (Twenty-fourth Congress). Knight retired from public life and was a delegate to the State constitutional convention in 1843. He died in Providence in 1854; interment was in Grace Church Cemetery.