Garner was born near Detroit, Red River County, Texas. He studied law, was admitted to the bar in 1890, and commenced practice in Uvalde, Uvalde County, Texas. He was a judge of Uvalde County from 1893 to 1896 and a member of the state House of Representatives from 1898 to 1902. He was elected as a Democrat to the Fifty-eighth and to the fourteen succeeding Congresses (March 4, 1903-March 3, 1933), and served as minority floor leader and as Speaker of the United States House of Representatives. He was reelected to the Seventy-third Congress on November 8, 1932, and on the same day was elected Vice President on the ticket headed by Franklin Delano Roosevelt. He was reelected Vice President in 1936 and served in that office from March 4, 1933 to January 20, 1941.
Garner switched alligances, however, and opposed Roosevelt's bid for a third term. In 1940 Garner ran against Roosevelt for the Democratic nomination but was defeated. Garner, always the character, once described the office of the vice presidency as being "not worth a bucket of warm piss" and that his decision to take it in the first place was "the worst damn fool mistake I ever made."
On Garner's 95th birthday (November 22, 1963), he spoke to President Kennedy over the telephone in regards to the upcoming 1964 Presidential campaign. Ironically, Garner vowed to support JFK's bid for as long as he himself was alive.