Fillmore, who served as vice president under Zachary Taylor, became the 13th president of the United States after Taylor's death in July 1850.

He became prominent in the Buffalo area as an attorney and politician, and was elected to the New York Assembly in 1828, and to the U.S. House of Representatives in 1832. Initially, he belonged to the Anti-Masonic Party, but became a Whig as the party formed in the mid-1830s.

In 1819, Abigail Powers took a teaching post at the private New Hope Academy, where her oldest pupil was 19-year-old Millard Fillmore. The world of knowledge and Fillmore's steady progress in it drew them together, and gradually the relationship of teacher and student evolved into romantic attachment. After a long courtship, Millard, aged 26, and Abigail, aged 27, were married on February 5, 1826.

In 1846, Fillmore was involved in the founding of what is now the University at Buffalo and became its first chancellor. The university has since evolved from a small medical school to a large research university. As of fall 2018, the university enrolled 31,503 students in 13 colleges, making it the largest public university in New York.

The cabinet officers, as was customary when a new president took over, submitted their resignations, expecting Fillmore to refuse and allow them to continue in office. But Fillmore had been marginalized by the cabinet members as vice president, and he accepted their resignations. Fillmore is the only president who succeeded by death or resignation not to retain, at least initially, his predecessor's cabinet.

When Supreme Court Justice Levi Woodbury died in September 1851 with the Senate not in session, Fillmore made a recess appointment of Benjamin Robbins Curtis to the high court. In December, with Congress convened, Fillmore formally nominated Curtis, who was confirmed. In 1857, Justice Curtis dissented from the Court's decision in the slavery case of Dred Scott v. Sandford and resigned as a matter of principle.

France, under Napoleon III, sought to annex Hawaii, but backed down after Fillmore issued a strongly worded message warning that "the United States would not stand for any such action."

Millard Fillmore was an animal lover and helped to establish the Society for Prevention of Cruelty to Animals (SPCA) branch in Buffalo, New York. Fillmore also had a sense of humor, and he revealed it in the naming of his ponies, Mason and Dixon--a reference to surveyors Charles Mason and Jeremiah Dixon, for whom the border between the Northern states and Southern states was named.

When Abigail Fillmore moved into the White House she was appalled that there was no library. With a special appropriation of $2,000 from Congress, she spent contented hours selecting books for a White House library in the Yellow Oval Room and invited writers such as William Thackeray, Charles Dickens, and Washington Irving to meet with her, essentially creating a White House literary salon.

Since the Constitution did not yet include a provision for replacing dead or departed vice presidents, the office remained vacant for the entirety of Fillmore's term.