Frank McCloud travels to a run-down hotel on Key Largo to honor the memory of a friend who died bravely in his unit during WW II. His friend's widow, Nora Temple, and wheelchair bound father, James Temple manage the hotel and receive him warmly, but the three of them soon find themselves virtual prisoners when the hotel is taken over by a mob of gangsters led by Johnny Rocco who hole up there to await the passing of a hurricane. Mr. Temple strongly reviles Rocco but due to his infirmities can only confront him verbally. Having become disillusioned by the violence of war, Frank is reluctant to act, but Rocco's demeaning treatment of his alcoholic moll, Gaye Dawn, and his complicity in the deaths of some innocent Seminole Indians and a deputy sheriff start to motivate McCloud to overcome his Hamlet-like inaction.

Two New York City longshoremen Axel Nordmann, an Army deserter and Tommy Tyler, an easy-going freight car loader whose growing friendship is threatened by Charles Malik, a notably repellent punk.