After briefly serving as the tenth vice president in 1841, John Tyler became the tenth president of the United States after William Henry Harrison's death in April 1841, just a month after the start of the new administration.

The office of vice president remained vacant after Tyler ascended to the presidency and was not filled until the next election.

William Henry Harrison's death caused an interesting problem for the federal government. For the first time ever, a President had died in office, and it wasn't entirely clear how the succession would play out. Amid the confusion, Tyler declared that he had full presidential powers. He arranged to be sworn in and gave an inaugural address while downplaying any talk of being a "temporary" President. Although opponents dubbed Tyler "His Accidency", his rise to power would eventually become the standard for presidential successions with the ratification of the 25th amendment in 1967.

When Tyler twice vetoed a national banking act that Henry Clay was trying to pass, the Whigs expelled him from their party--a first for a sitting president.

Tyler decided to keep Harrison's entire cabinet even though several members were openly hostile to him. On September 11, 1841, after his second bank veto, members of the cabinet entered Tyler's office one by one and resigned--an orchestration by Henry Clay to force Tyler's resignation. The only exception was Daniel Webster, who remained to demonstrate his independence from Clay. When told by Webster that he was willing to stay, Tyler is reported to have said, "Give me your hand on that, and now I will say to you that Henry Clay is a doomed man."

Although it was then unprecedented to reject a president's nominees for his Cabinet, due to Tyler's lack of support from either party in Congress, four of Tyler's Cabinet nominees were rejected, the most of any president. These were Caleb Cushing (Treasury), David Henshaw (Navy) James Porter (War), and James S. Green (Treasury). Tyler repeatedly renominated Cushing, who was rejected three times in one day on March 3, 1843.

Tyler vetoed 10 bills (6 regular vetoes and 4 pocket vetoes), but only 9 were successful. On the last day of Tyler's term in office, on March 3, 1845, Congress overrode his veto of a minor bill relating to revenue cutters, making him the first president to see his veto of legislation overridden by Congress.

A House select committee headed by John Quincy Adams, an ardent abolitionist who disliked slaveholders like Tyler, condemned the president's use of the veto and assailed his character. While the committee's report did not formally recommend impeachment, it clearly established the possibility, and in August 1842, the House endorsed the committee's report. However, the Whigs were unable to pursue further impeachment proceedings after losing control of the House in the elections of 1842.

Letitia Tyler died peacefully, aged 51, in the evening of September 10, 1842 from a stroke. She was taken to Virginia for burial at the plantation of her birth. Letitia, along with Caroline Harrison and Ellen Wilson, are the only first ladies to have died in the White House.

On January 20, 1842, 21-year-old Julia Gardiner was introduced to President John Tyler at a White House reception. After the death of his first wife, Letitia Christian Tyler, on September 10, 1842, Tyler made it known that he wished to pursue a relationship with Julia. Initially, the high-spirited and independent-minded northern beauty felt little attraction to the grave, reserved Virginia gentleman, who was thirty years her senior. She rejected his first proposal at a White House Masquerade Ball, as well as several subsequent proposals, but she eventually relented and married him in 1844, at the age of 24.