After graduating from the U.S. Military Academy at West Point in 1875, Bliss served in various military assignments, including that of instructor at West Point and military attaché at the U.S. legation in Madrid. During the Spanish-American War (1898), Bliss was chief of staff under General James H. Wilson in Puerto Rico and later served in Cuba. Promoted to the rank of brigadier general, he negotiated the U.S.–Cuban reciprocity treaty (1902). After service as commandant of the Army War College (1903–05) and in the Philippines (1905–09), he drew various staff assignments and in 1915 was promoted to major general.

With the United States' entry into World War I in 1917, Bliss was made general and chief of staff. In that position he promptly expanded and upgraded the Army to battle-readiness and resisted attempts to divide the U.S. force among the various Allied commands. At the appointment of President Woodrow Wilson, he sat on the Allied Supreme War Council and was a delegate to the peace conference at Versailles. An ardent supporter of Wilson's worldview, Bliss promoted the Fourteen Points, American participation in the League of Nations, and international arms control.