He was born at "Beargrass", Jefferson County, Kentucky, near the present site of Louisville, and attended Transylvania University. He was admitted to the bar in 1802, and was a member of the state House of Representatives from 1804-1806 and again in 1819. He was elected as a Democratic-Republican to the Tenth and to the five succeeding Congresseses (March 4, 1807-March 3, 1819). He was chairman of the Committee on Claims and the Committee on Expenditures in the Department of War.
Johnson was commissioned a Colonel of Kentucky Volunteers and commanded a regiment in engagements against the British in Lower Canada in 1813. He was elected to the United States Senate to fill the vacancy caused by the resignation of John J. Crittenden, and was reelected and served from December 10, 1819 to March 3, 1829. He was an unsuccessful candidate for reelection in 1829.
He was chairman of the Committee on Post Office and Post Roads. He was elected to the Twenty-first and to the three succeeding Congresses (March 4, 1829-March 3, 1837) He was chairman of the Committee on Post Office and Post Roads and Committee on Military Affairs. He was chosen Vice President by the Senate on February 8, 1837, no candidate having received a majority of the electoral vote, and served under President Martin Van Buren from March 4, 1837, to March 3, 1841.
Johnson was a member of the state House of Representatives in 1850, but he died in Frankfort, Kentucky soon after taking his seat. He was intered in the Frankfort Cemetery.
His brothers James and John Telemachus and his nephew Robert Ward Johnson were all members of the House of Representatives, and, in the case of Robert Ward, a Senator as well.
After his first two wives died, the old Jacksonian Democrat had a common-law marriage with a former slave, Julia Chinn, whom he had inherited from his father. Together they had two daughters, Adaline Chinn Johnson and Imogene Chinn Johnson.