Chicago, circa 1927. Naive Roxie Hart visits a nightclub, where star Velma Kelly performs, with Fred Casely, a lover she hopes will get her a vaudeville gig. After the show, Velma is arrested for killing her husband and sister, Veronica, after finding them in bed together. Later, Fred reveals that he lied about his connections in order to sleep with Roxie. She shoots Fred three times. Roxie convinces her husband Amos to take the blame, telling him it was a burglar and that he needn't worry, he'll get off. When the officer points out that the victim is Fred Casely, who sold the Harts furniture, Amos abandons his lie and says Casely was dead when he got home. Roxie is sent to the Cook County Jail.
Upon her arrival, she is sent to Murderess' Row to await trial — under the care of the corrupt Matron "Mama" Morton, who takes bribes and supplies her prisoners with cigarettes and contraband. Roxie meets Velma, and learns the stories behind the other women in Murderess' Row.
Roxie decides that she wants to engage Velma's lawyer, Billy Flynn, and convinces her husband to talk to him. Flynn and Roxie manipulate the press at a press conference, reinventing Roxie's identity to make Chicago fall in love with her. Roxie becomes the new infamous celebrity of the Cook County Jail, much to Velma's disgust and Mama's delight.
Velma, desperate to get back into the limelight, tries to talk Roxie into opening a vaudeville act with her once they get out of jail. In revenge for an earlier mocking, Roxie haughtily refuses, and Roxie and Velma become locked in a rivalry to outdo each other in stardom.
Roxie manages to steal back the limelight by claiming to be pregnant, which is falsely confirmed by a doctor (whom it is implied she seduced). Roxie witnesses the execution by hanging of another inmate who has lost her last appeal, which fuels Roxie's desire to be free. Roxie and Billy plan their strategy to find her innocent using her star power and sympathy vote. Her trial becomes a media spectacle, fed on the sensationalist reports of newspaper reporter and radio personality Mary Sunshine. The trial goes Roxie's way, until Velma shows up with Roxie's diary and, in exchange for amnesty, reads incriminating entries that Roxie claims not to have written. Using some quick talking, Billy manages to get Roxie off the hook and she is proclaimed innocent. However, Roxie's publicity is short lived: as soon as the trial concludes, the public's attention turns quickly to a new murderess. Roxie leaves the courthouse after discovering that Billy wrote the false diary entries, and sent the journal to Velma to get her off death row. Roxie reveals to Amos she faked her pregnancy for the fame. It is implied, but never stated, that Amos leaves her at this point.
With nothing left, Roxie once more sets off to find a stage career, with little success. However, she is soon approached by Velma, also down on her luck, who is willing to revive a two-person act with Roxie. Roxie refuses at first, still not over the hate they shared for each other while in prison, but relents when Velma points out that "there's only one business in the world where that's not a problem" - show business. The two murderesses, no longer facing jail time, finally become the enormous successes they have been longing to be. The film concludes with Roxie and Velma receiving a standing ovation from an enthusiastic audience that includes Mama Morton and Billy Flynn.
