He was born in Fox Meadows (later Scarsdale), Westchester County, New York. He graduated from Columbia College in New York City, in 1795. He studied law, and was admitted to the bar in 1797, practicing in New York City;.

Tompkins was a delegate to the state constitutional convention in 1801, a member of the state Assembly in 1803, and was elected to the United States Congress, but resigned before the beginning of the term to accept an appointment as associate justice of the state supreme court, in which capacity he served from 1804 to 1807. He was Governor of New York from 1807 to 1817. He declined an appointment as United States Secretary of State by President James Madison. He was elected Vice President on the ticket with James Monroe in 1816, and was reelected in 1820, serving from March 4, 1817 to March 3, 1825.

In 1815 Tompkins established a settlement and along the eastern shore of Staten Island that came to be called Tompkinsville. In 1817 he built a dock along the waterfront in the neighborhood and began offering daily steam ferry service between Staten Island and Manhattan.

He was a delegate to the state constitutional convention in 1821, serving as its president. He died in Tompkinsville, three months after retiring as Vice President, and was interred in the Minthorne vault in St. Mark's Churchyard, New York City.

There is evidence that Daniel Tompkins's middle name was Decius. However, others believe that he added the middle initial "D" (which stood for nothing) while a student at Columbia College, to distinguish himself from another Daniel Tompkins there.

Tompkins County, Tompkins Square Park in Manhattan, and the Town of Tompkins are named after him. Daniel D. Tompkins gained a slight notoriety in 20th century cinema, when he was mentioned by Kris Kringle in Miracle on 34th Street during his psychological evaluation. (However, the screenplay erred: Kringle mentions that Tompkins served as vice-president under John Quincy Adams).

Trivia: Tompkins had the shortest post-Vice Presidency: 3-months (March 3 until his death on June 11, 1825).

Preceded by: Morgan Lewis Governor of New York 1807-1817 Succeeded by: John Tayler Preceded by: Elbridge Gerry Republican Party vice presidential candidate 1816 (won), 1820 (won) Succeeded by: John C. Calhoun(a) Preceded by: Elbridge Gerry Vice President of the United States March 4, 1817 - March 3, 1825 Succeeded by: John C. Calhoun (a) The Republican Party party splintered in the election of 1824. Calhoun was the most prominent of several Republican vice presidential candidates, winning more than six times as many votes as his nearest competitor.