Tyler was elected Vice-President in November of 1840 on a ticket with Harrison. The two men were not close even though they had been born in the same county (seventeen years apart). Harrison did not seek Tyler's advice on the selection of his cabinet and Tyler went to his home in Virginia after he was sworn in as Vice-President, where he remained for the rest of Harrison's 31 day presidency.
After getting the news of Harrison's death, Tyler arrived in Washington at 4:00 a.m. on April 6, 1841. Although there was no precedent about what happened upon the death of a sitting President, Tyler was firmly of the view that he was, in title and and fact, President of the United States. He had himself sworn in as president in his hotel room. Later that day, Tyler called the Cabinet into session. Secretary of State Daniel Webster informed him of Harrison's practice of making policy by a majority vote and said that the Cabinet expected Tyler to continue this practice. Tyler refused to follow this practice. He told his cabinet: "I beg your pardon, gentlemen. I am very glad to have in my Cabinet such able statesmen as you have proved yourselves to be. And I shall be pleased to avail myself of your counsel and advice. But I can never consent to being dictated to as to what I shall or shall not do. I, as president, shall be responsible for my administration. I hope to have your hearty co-operation in carrying out its measures. So long as you see fit to do this, I shall be glad to have you with me. When you think otherwise, your resignations will be accepted."
Tyler delivered a form of inaugural address on April 9, 1841, in which he stated his commitment to a belief in limited federal power. Tyler's claim to be president was met with opposition by some of the members of Congress. These included fellow Whig John Quincy Adams, who saw Tyler as a caretaker under the title of "Acting President". Whig leader Henry Clay felt that as his party's leader, Tyler should follow the party's dictates under Clay's direction. In Clay's view Tyler was still the vice-president, akin to a regent.
Tyler's opponents referred to him by many mocking nicknames, including "His Accidency". But Tyler never wavered from his conviction that he was the rightful president. His political opponents sent him correspondence addressed to the "vice president" or "acting president". When that happened, Tyler would send it back unopened.
At first Tyler signed legislation passed by the new Whig Congress into law. This included a bill granting squatters sovereignty to settlers on public land, a Distribution Act, a new bankruptcy law, and the repeal of the Independent Treasury enacted under his predecessor Martin Van Buren. But trouble loomed when Congress addressed the question of a National Banking Act. Tyler vetoed Henry Clay's legislation for a national banking act, not once, but twice. The second bill had been tailored to meet the objections that Tyler had stated in the first veto, but he still vetoed it. Tyler proposed an alternative plan to be known as the "Exchequer", but Clay would not agree to the compromise.
On September 11, 1841, following the second bank veto, members of the cabinet entered Tyler's office after another. This was orchestrated by Clay to force Tyler's resignation and place a Clay supporter, Senate President pro tempore Samuel L. Southard, in the White House. Only Secretary of State Webster remained in Cabinet so as to finalize what became the 1842 Webster–Ashburton Treaty, and also because he wanted to demonstrate his independence from Clay. (Webster was considering running for President in 1844).
Tyler did not resign or give in, so on September 13, 1841, the Whigs in Congress expelled Tyler from their party. Tyler was criticized by Whig newspapers and he even received many letters threatening his assassination. Whigs in Congress were so angry with Tyler that they refused to allocate funds for the repair of the White House, which had fallen into disrepair.
In 1842 an economic bubble had burst, the result of land speculation, that caused a collapse of the financial sector and a subsequent depression. In a recommendation to Congress, Tyler recommended that Congress override the Compromise Tariff of 1833 and raise rates beyond the 20 percent recommended limit. But a defiant Whig Congress would not raise tariffs to that extend nor in a way that would affect the distribution of funds to states. In June 1842 they passed two bills that would raise tariffs and unconditionally extend the distribution program. Tyler vetoed both bills, burning any remaining bridges between himself and the Whigs. Congress tried again, combining the two into one bill, but Tyler vetoed it again. Congress failed to override the veto. Whigs in Congress narrowly passed a bill restoring tariffs to 1832 levels. Tyler signed the Tariff of 1842 on August 30, but he used a pocket veto for a separate bill to restore distribution of funds to the states.
Shortly after the tariff vetoes, Whigs in the House of Representatives initiated the first impeachment proceedings against a president. The proceedings were commenced not because of anything illegal that Tyler had done, but mainly because of the vetoes and because of Tyler's unwillingness to follow the directions of the Whig Party. Until the presidency of Andrew Jackson, presidents rarely vetoed bills, and then, generally only on constitutional ground. Tyler disagreed the Whigs' opinion that the presidency should allow Congress to make decisions regarding policy. Whig Congressman John Botts introduced a resolution on July 10, 1842 which set out several charges against Tyler and called for a nine-member committee to investigate his behavior. This was a pre-requisite to a formal impeachment recommendation.
Although he was no fan of John Tyler, Henry Clay took a more principled stance and had Botts' resolution tabled until the following January (of 1843). At that time Botts' resolution was rejected by a House vote of 127 against to 83 for.
A House select committee, headed by former President and now Representative John Quincy Adams, condemned Tyler for his use of the veto. Adams was an ardent abolitionist, and he disliked Tyler, among other reasons for the fact that Tyler was a slaveholder. The committee's report did not formally recommend impeachment, but did not foreclose on the possibility. In August 1842, by a narrow vote of 98–90, the House endorsed the committee's report. Adams sponsored a constitutional amendment to change both houses' two-thirds requirement (for overriding vetoes) to a simple majority. Neither the House nor the Senate supported such a measure.
The Whigs were unable to pursue further impeachment proceedings in the subsequent 28th Congress. They retained a majority in the Senate but lost control of the House. Near the end of Tyler's term in office, on March 3, 1845, Congress overrode his veto of a minor bill about revenue cutters (ships used to collect tariffs). This was the first time in US history that any presidential veto had been over-ridden. Ironically it was this same Congress that passed Tyler's plan for the annexation of Texas. The veto override occurred on the last full day of Tyler's presidency. The following day his successor, James K. Polk, was sworn in as the 11th President.