John Caldwell Calhoun was born March 18, 1782, near Abbeville, South Carolina. He graduated from Yale College in 1804 and was admitted to the South Carolina bar in 1807 but only practiced law briefly. Calhoun was elected to the South Carolina House of Representatives in 1808 and then served in the U.S. House of Representatives as a Democratic-Republican from 1811 to 1817. In the House, Calhoun distinguished himself as one of the "War Hawks" who supported President James Madison's efforts to declare war on Britain in 1812.

President James Monroe appointed Calhoun secretary of war, and he served for the entirety of Monroe's two administrations from 1817 to 1825. As secretary of war, he was considered an able administrator, overseeing a review of the department's operations and accounts. In the 1824 election, Calhoun initially hoped to be considered for the presidency, but recognizing his inability to compete with John Quincy Adams, Andrew Jackson, Henry Clay, or William Crawford, he ultimately accepted the vice presidency. When no presidential candidate won an electoral majority, the House of Representatives chose John Quincy Adams as President despite Jackson's winning the popular votes. Adams in turn selected Clay as his secretary of state. Calhoun was deeply offended by this perceived "corrupt bargain," in which people alleged that Clay had engineered Adams' election in the House in exchange for the appointment. Calhoun and Adams also agreed politically on few issues and had a tense relationship, which only deteriorated during the administration. In the election of 1828, Calhoun was reelected as vice president on a ticket with Andrew Jackson. At first Jackson and Calhoun seemed to work together more smoothly than Calhoun had with Adams, but that situation was short lived. They disagreed over policy, especially the policy of nullification. In response to a tariff that negatively impacted the rural South, Calhoun advocated the idea that the United States was a compact between states, and if a state disagreed with federal policy, it could veto any federal act that intruded on state sovereignty. President Jackson vehemently disagreed.

Calhoun also had a personal falling out with Jackson over Secretary of War John Eaton and his wife Peggy. Scandalous stories had circulated about Peggy Eaton, whose first husband had died under mysterious circumstances—allegedly committing suicide due to Peggy's infidelity with Eaton. Cabinet wives, including Calhoun's wife, Floride, regarded Peggy Eaton with abhorrence and conspicuously shunned her. In that snubbing, President Jackson saw the kind of vicious persecution that he believed had hounded his own wife Rachel to her death. Jackson came to blame Calhoun for the situation, accusing him of treachery and initiating an angry correspondence that severed social relations between the two men. This situation allowed Martin Van Buren to win favor with Jackson and ultimately replace Calhoun as vice president in the 1832 election. Calhoun became the first vice president to resign his position in December 1832; he then served in the U.S. Senate from 1832 to 1843. During his years in the Senate, he ceased to be a nationalist and became a staunch sectionalist and outspoken defender of slavery and the South. In 1844, President John Tyler appointed Calhoun secretary of state, and Calhoun served in that position for one year. He was reelected to the Senate in 1845 and served until his death on March 31, 1850.