John Nance Garner was born on November 22, 1868, in Red River County, Texas. As a young man, he worked odd jobs and played semipro baseball before departing for Tennessee, where he spent a semester at Vanderbilt University. Health problems prompted him to move back to Texas, where he studied law and continued to supplement his income playing baseball before gaining admittance to the bar in 1890. Shortly afterwards, he was diagnosed with tuberculosis and moved to Uvalde, Texas, for the dry climate. In Uvalde, he served as a county judge and a member of the state legislature before winning election to the U.S. House of Representatives in 1902.

Garner used the early years of his House tenure to make friends and establish a record of party loyalty that helped him ascend to prominent positions on the Ways and Means Committee as well as the Committee on Committees, which handled committee appointments. He himself authored few bills throughout his long tenure in the House but commanded considerable influence through his wealth of political friendships and legislative skills. When the Democrats won a slim majority in 1931, Garner became Speaker of the House.

Having emerged as a well-known party leader, "Cactus Jack" was as a prominent contender for the presidential nomination in 1932. Although he commanded significant support, he did not have enough to capture the nomination. The front-runners, however, did not have the necessary two-thirds majority to win the nomination. Garner's campaign manager, fellow Texan Sam Rayburn, held a meeting with Franklin Roosevelt's campaign manager, and they reached an agreement to transfer Garner's delegates to Roosevelt. Garner was subsequently offered the vice presidency, although the two later denied that the arrangement was the product of political deal-making. Garner commented that the vice presidency "might be a nice way for me to taper off my career." He spent much of the campaign in Uvalde and made only two speeches throughout the campaign, which Roosevelt won with a decisive victory.

President Roosevelt had an extremely ambitious agenda for his first term and used Garner's knowledge and experience to help him execute it. Throughout the first term, Garner was an invaluable member of the new administration as it pursued revolutionary solutions to address the Great Depression. Garner used his political contacts in both the House and Senate to assist passage of Roosevelt's agenda. As presiding officer of the Senate, he sometimes descended to the Senate floor to personally lobby for bills. Although he provided essential assistance to Roosevelt throughout the first term, differences between the two men began to sour the relationship. While Garner generally supported emergency legislation to address the Depression, he was not comfortable with all of the New Deal programs. He was particularly critical of the Wagner Labor Relations Act, the Social Security Act, and the Revenue Act. Furthermore, Roosevelt's attempts to direct the legislative agenda offended Garner's deeply held belief in the importance of an independent Congress. While he was renominated in 1936, his role within the administration changed profoundly.

In late 1936, Roosevelt's approach to labor strikes led to a heated exchange between the President and Garner, and from then on the vice president became more a figure of opposition than cooperation. Garner opposed Roosevelt's "court-packing" plan and was noticeably absent during the congressional debates regarding the proposal. Roosevelt also went against Garner's advice and aggressively tried to unseat conservative Democrats in the 1938 midterm elections. The President's intervention earned him substantial enmity from conservative members of his own party, many of them close friends of Garner, and helped stall his legislative agenda.

When Roosevelt began to hint at the possibility of a third term, Garner was aghast and declared his own candidacy in December 1939. Although he attracted some support, Garner knew that Roosevelt would take the nomination if he sought it. The increasing instability in Europe assured Roosevelt's nomination and eventual election. Garner did not reconcile with Roosevelt, however, and did not even vote in the 1940 election.

John Nance Garner was an exceptionally powerful vice president in both a constructive and obstructionist sense. He initially helped pilot Roosevelt's ambitious proposals through Congress but later came to embody the opposition of conservative Democrats to the New Deal. Although he famously remarked that the vice presidency was "not worth a bucket of warm spit," Garner derived significant power from his understanding of the limitations and possibilities of his office. His powers of persuasion and parliamentary skill enabled him to make the most of an office with so little formal power. He was also the last vice president to act primarily as a legislative officer, as the increasingly internationalist role of the country and advances in communications made the vice president more active and visible.

Garner retired to Uvalde after the 1940 election and lived there until he died just before his 99th birthday on November 7, 1967.