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Johnny O'Clock is a junior partner in a posh casino with Guido Marchettis. Complicating their longtime working relationship is Guido's wife Nelle, who is still in love with former boyfriend Johnny. She gives Johnny an expensive custom pocket watch, the twin of a birthday present she gave her husband, except Johnny's has a romantic engraving on the back.
Johnny gives the watch, along with a rejection note, to Harriet Hobson, a hat-check girl at the casino, to return to Nelle. Harriet, however, apparently commits suicide using gas. Her sister Nancy shows up to find out what happened. She becomes attracted to Johnny. They eventually learn from Police Inspector Koch that Harriet was killed by poison.
Harriet was dating Chuck Blayden, a crooked cop who is trying to persuade Guido to let him take Johnny's place. When Blayden also turns up dead, Koch suspects that either Johnny or Marchettis is responsible.
Though Johnny tries to resist, little by little, he falls for Nancy. When Koch shows both Johnny and Marchettis Johnny's watch and note, Johnny tells Nancy their relationship is through and takes her to the airport. As he is driving away, however, he narrowly survives a drive-by shooting, and Nancy realizes he was only trying to protect her. She refuses to leave him.
Johnny decides to flee to South America with Nancy, but not before brazenly cashing in his share of the casino. Marchettis pulls out a gun when Johnny's back is turned. They shoot it out; Marchettis is killed and Johnny wounded. Afterward, Nelle offers to testify it was self-defense, but only if he will come back to her. He refuses, so she tells Koch it was cold-blooded murder. Johnny's first instinct is to run away, but Nancy convinces him to give himself up.

Nancy