Bendix was born in Manhattan, the only child of Oscar and Hilda (Carnell) Bendix, and was named William after his German paternal grandfather. His uncle was composer, conductor, and violinist Max Bendix. In the early 1920s, Bendix was a batboy for the New York Yankees and said he saw Babe Ruth hit more than 100 home runs at Yankee Stadium. However, he was fired after fulfilling Ruth's request for a large order of hot dogs and soda before a game, which resulted in Ruth being unable to play that day. He worked as a grocer until the Great Depression.
Bendix began his acting career at age 30 in the New Jersey Federal Theatre Project. He made his film debut in 1942. He played in supporting roles in dozens of Hollywood films, usually as a warm-hearted gangster, detective or serviceman. He began with appearances in films noir, including a supporting role in The Glass Key (1942), which featured Brian Donlevy, Alan Ladd and Veronica Lake in the leads. He soon gained attention after appearing in Alfred Hitchcock's Lifeboat (1944) as Gus, a wounded and dying American sailor. He was the top-billed lead in The Hairy Ape (1944) based upon the Eugene O'Neill play, also starring Susan Hayward and Dorothy Comingore.
Bendix's other film roles include his portrayal of Babe Ruth in The Babe Ruth Story (1948) – a film roundly considered one of the worst sports biopics in film history and Sir Sagramore opposite Bing Crosby in A Connecticut Yankee in King Arthur's Court (1949), in which he took part in the trio, "Busy Doing Nothing". He played Nick the bartender in the film version of William Saroyan's The Time of Your Life (1948) starring James Cagney. Bendix had appeared in the stage version, but in the role of Officer Krupp (a role played on film by Broderick Crawford). He was cast in The Blue Dahlia (1946), appearing for the second time alongside Ladd and Lake. He also starred in a film adaptation of his radio program The Life of Riley (1949).

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