Upon his father's death in 1779, John Wheelock assumed the presidency of the College, despite the fact that he was neither an academic nor a minister.

During the latter half of Wheelock's tenure, he became embroiled in a dispute with Dartmouth’s Board of Trustees.

The case, Dartmouth College v. Woodward, went through various judicial courts, before the United States Supreme Court decided in the Board's favor in 1819, the result of a brilliant peroration by Dartmouth alumnus Daniel Webster, class of 1801, who had, ironically, graduated under Wheelock's tenure.

However, by this time, Wheelock, who had been forced out of the presidency in 1815 by failing health and poor relations with the Board, had died.

Wheelock died on April 4, 1817, and is buried near his father in the cemetery in Hanover, NH.