Born Melvyn Edouard Hesselberg in Macon, Georgia, he had a long film career, stretching from 1931 until just before his death. He was the hero in the 1932 horror film The Vampire Bat and the sophisticated leading man in 1935's She Married Her Boss. His first major role was opposite Greta Garbo in Ninotchka in 1939, and he starred with her again in 1941's Two-Faced Woman (they had also appeared together in 1932 in As You Desire Me.
During World War II, Douglas worked first as a director of the Office of Civilian Defense, before he left to serve in the United States Army. He returned to such comedy roles as in Mr. Blandings Builds His Dream House, a role that was made for him. As Douglas grew older, he took on the older-man and father roles, in such movies as The Americanization of Emily, Hud, The Candidate and I Never Sang for My Father, for which he was nominated for the Academy Award for Best Actor.
Douglas was married for fifty years to actress-turned-politician Helen Gahagan Douglas. As a two-term Congresswoman, she was Richard Nixon's opponent for the United States Senate seat from California in 1950. Nixon accused Gahagan of being a Communist because of her opposition to the House Un-American Activities Committee. Nixon went so far as to call her "pink right down to her underwear". It was Gahagan who gave Nixon his epithet "Tricky Dick."