Four friends enrolled at the Glendale, Arizona campus of Midwestern University - Brick (Keith), Al (Madison), Ronnie (Kerwin Mathews) and Roy (Alvy Moore) - visit the Harold's Club casino in Reno, Nevada during a weekend trip.
Recently paroled from prison, legendary burglar "Doc" Riedenschneider, with funding from Alonzo Emmerich, a crooked lawyer, gathers a small group of veteran criminals together in the Midwest for a big jewel heist.
When an employee at an illegal gambling den dies suspiciously, her sister, Nancy, looks into the situation and falls for Johnny O'Clock, a suave partner in the underground casino. Selfish and non-committal by nature, Johnny slowly begins to return Nancy's affection and decides to run away with her, but conflict within his business threatens their plans. As Johnny tries to distance himself from the casino, his shady past comes back to haunt him.
A corrupt D.A. with governatorial ambitions is annoyed by an investigative reporter's criticism of his criminal activities and decides to frame the reporter for manslaughter in order to silence him.