After graduating from Yale in 1853, White studied in Europe for the next three years, serving also as attaché at the U.S. legation at St. Petersburg, Russia, in 1854–55. He returned to the United States to become professor of history and English literature at the University of Michigan, Ann Arbor. In 1865 White's dream of a state university for New York—based on liberal principles with reference to religion, coeducation, race, and the teaching of science unhampered by religious dogma—was realized when Cornell University was chartered. As Cornell's first president (1868), White devoted his energies and much of his wealth for the next 17 years to assure its success and future growth.

White served on numerous government commissions and was U.S. minister to Germany (1879–81) and Russia (1892–94) and ambassador to Germany (1897–1902). In 1899 he was president of the U.S. delegation at the Hague Peace Conference (Hague Convention). His published works include A History of the Warfare of Science with Theology in Christendom (1896) and Seven Great Statesmen in the Warfare of Humanity with Unreason (1910).