Born in Savannah, Georgia, Coburn was a theater manager by the age of 17. He later moved on to acting and made his debut on Broadway in 1901. Coburn formed an acting company with his wife in 1906, and in addition to managing the company, the couple performed frequently on Broadway. After his wife's death in 1937, Coburn relocated to Los Angeles, California and began acting in films.

He won an Academy Award for Best Supporting Actor for his role in The More the Merrier in 1943. He was also nominated for his roles in The Devil and Miss Jones in 1941 and The Green Years in 1946.

In the 1940s, Coburn served as vice-president of the Motion Picture Alliance for the Preservation of American Ideas, a right-wing group opposed to the presence of Communists in Hollywood. His virulent leadership of the blacklist of anyone with any connection to anti-Fascism, supported by such Academy-Award nominees as Adolph Menjou and Ginger Rogers, led to a myriad of talented actors, writers and directors driven from Hollywood and deprived of their livelihood during the witchhunt.

His other film credits include Of Human Hearts (1938), The Lady Eve (1941), Kings Row (1942), The Constant Nymph (1943), Heaven Can Wait (1943), Wilson (1944), Impact (1949), The Paradine Case (1947) and Gentlemen Prefer Blondes (1953).

He died from a heart attack in New York, New York.

Charles Coburn has a star on the Hollywood Walk of Fame for his contributions to motion pictures at 6240 Hollywood Boulevard.