Johnny Handsome (Mickey Rourke) is a small time crook with a grotesquely deformed face. When thrown in prison for a crime he did not do, he befriends a kind doctor (Forest Whitaker) who believes that Handsome would change his ways if he had a normal face. Handsome undergoes plastic surgery and reappears unrecognisable to anyone who knows him.

When given parole, it seems that Johnny plans to live a straight life... until the past catches up and shows that he only has one aim: to fullfil his revenge on the man who set him up.