Thomas Riley Marshall was born March 14, 1854, in North Manchester, Indiana, to Daniel and Martha Patterson Marshall. Marshall's father was a country doctor who spent much of his time caring for his mother, who suffered from tuberculosis. Marshall attended Wabash College and studied law after graduating, gaining admittance to the Indiana bar in 1875. He lived with his mother until shortly before he married Lois Kimsey in 1895.

His family was traditionally Democratic, and Marshall was involved in politics from a young age. However, he did not successfully seek public office until 1908, when he was unexpectedly elected governor of Indiana.

Indiana was a pivotal swing state at the time, carried by every successful presidential candidate since 1880. Marshall, as the well-liked governor of a strategically important state, was in good position to advance to the national stage. Although Woodrow Wilson would have preferred a more progressive pick, he reluctantly chose Marshall because he balanced the ticket well. Marshall initially considered rejecting the offer because the job did not pay enough, but Mrs. Marshall's eagerness to go to Washington induced him to accept. With the Republican Party bitterly divided between President William Taft and former President Theodore Roosevelt, Wilson won in a landslide.

Marshall assumed that the job of vice president offered more responsibility and was disappointed when he realized the limits of his formal duties. Furthermore, his jovial disposition contrasted sharply with the serious intellectualism of Wilson, who had little to do with Marshall. President Wilson rarely consulted his vice president, and they often went months between meetings. Wilson was at least true to his words, having written in his 1885 book, Congressional Government, that the office of vice president "is one anomalous insignificance and curious uncertainty."In spite of his limited role, Marshall was well-liked nationally, and the Democrats renominated him in 1916. He became the first vice president elected to a second term since John C. Calhoun in 1828. The vice president dutifully supported Wilson's actions before and during World War I and briefly presided over the cabinet when Wilson left on a lengthy trip to negotiate the terms of peace in Europe. However, Marshall gave up his presiding role, citing a conflict of interest in being both presiding officer of the Senate and the cabinet.

When President Wilson suffered a stroke in October 1919 and was almost completely incapacitated, Marshall remained largely unaware of his condition and reluctant to take any decisive action. He did not attempt to preside over cabinet meetings, thinking that such action might be viewed as an attempt to usurp Wilson's authority. While the Constitution clearly stated the vice president should take office if the President was unable "to discharge the Powers and Duties of the said Office," there was no established process for carrying this out in such a case. Although Marshall would have had substantial Congressional support had he asserted authority, he declined to do so. The final months of the Wilson administration passed in curious uncertainty, with Wilson unable to serve but unwilling to relinquish control. Such issues of presidential disability were later clarified with the adoption of the 25th amendment in 1967.

Marshall briefly pursued the nomination for President in 1920 but attracted limited support. He retired to Indiana afterwards and passed away on June 1, 1925.