Although educated as an attorney, his hulking 6 ft 5 in (196 cm) presence, craggy face, and croaking voice had him often typecast as brainless athletes, tough guys, thugs, and gangsters.

Memorable roles included Moose Malloy in Murder, My Sweet (1944), Splitface in Dick Tracy (1945), Yusuf in Sinbad the Sailor (1947), and "The Strangler" in Night and the City (1950).

[citation needed] Mazurki was discovered by Josef von Sternberg and given a bit part in his film The Shanghai Gesture (1941).

Possibly his best-known role was as the slow-witted but dangerously obsessed thug Moose Malloy in the lurid film noir Murder, My Sweet (1944).

[citation needed] In addition to his film work, Mazurki made guest appearances on many popular television shows, among them My Friend Flicka (as a wrestler facing Gene Evans's character "Rob McLaughlin"), The Untouchables, Bachelor Father, Daniel Boone, Gilligan's Island, The Munsters, I Dream of Jeannie, Bonanza, and Gunsmoke, to name just a few.

His final film role, that of "Don Taglianeti", is in the low-budget comedy Mob Boss, which was released just two months before he died.