When Martin Van Buren lost his 1840 bid for reelection, he never considered it the end of his political career. In fact, over the next four years he emerged as the favorite for the Democratic nomination in 1844. Van Buren, however, stumbled on his way to the nomination. Having lost the presidential election in 1840, many in his party saw him as a weak candidate.

In addition, many Democrats supported the annexation of Texas during the early 1840s, much to the chagrin of numerous fellow party members who opposed the admittance of another slave state to the Union. Looking to secure his status as the favorite for the Democratic nomination, Van Buren tried to bridge the divide in his party by stating in the spring of 1844 that while he did not support the immediate annexation of Texas, he certainly welcomed it at some future date. This was a political miscalculation. The pro-annexation strength in his party—some Democrats threatened to bolt the party if Van Buren won the nomination—was much stronger than he realized. Even some of his long-time allies, like Thomas Ritchie, head of Virginia's Democrats, left Van Buren's side after he revealed his position on Texas. The final blow came when Andrew Jackson proclaimed himself in favor of immediate annexation and suggested that Van Buren step aside.

At the 1844 Democratic national convention in Baltimore, support for Van Buren's candidacy disintegrated. Democrats instead turned to the pro-annexation James K. Polk of Tennessee, who had the blessing of former President Jackson to boot. Although disappointed at his failure to win the nomination, Van Buren vigorously supported Polk's candidacy, which helped the Democrat to victory over Whig candidate Henry Clay in 1844. This closing of party ranks, however, did not signal easy relations between Polk and Van Buren. The former President and his allies believed that Polk owed his election largely to the Van Buren's efforts—and therefore expected to receive an important post in the Polk administration. This did not occur—although Polk offered Van Buren the ministership to London, an appointment Van Buren refused—and relations between Van Buren and Polk (and their allies) soured.

Four years later, the question of new states and slavery had become even more divisive. Van Buren headed a splinter group—the Free-Soil Party—comprised of dissatisfied Democrats, Whigs who opposed their party's nominee, General Zachary Taylor, and members of the anti-slavery Liberty Party. The Free Soil Party's main issue was opposition to the extension of slavery to the new Western territories. Van Buren had little hope of victory. Taylor won the election convincingly, although the Free Soilers ran well in a number of northern states, including New York, Massachusetts, Ohio, and Illinois.

The 1848 election effectively marked the end of Van Buren's active political career. He wrote his memoirs in the early 1850s, as well as a milestone study of the organization of American political parties. He traveled extensively, including a trip to Europe, and spent time with his surviving children and grandchildren, delighting in their company. Van Buren lived to see the coming of the Civil War and he supported President Lincoln's decision to resist secession with force. Martin Van Buren died in 1862, at age seventy-nine.