It's 1920s Chicago and Roxie Hart (RENEE ZELLWEGER) is an aspiring singer and performer who's hoping that Fred Casely (DOMINIC WEST) can get her into show business. Unfortunately, he's using her just for sex. Shocked, upset and feeling used, she then shoots and kills him. Despite the efforts of her supportive, but passive husband, Amos (JOHN C. REILLY), she's sent to prison to await her trial.
There, she meets Mama Morton (QUEEN LATIFAH), the prison official who runs the place through bribes and other forms of corruption, as well as Velma Kelly (CATHERINE ZETA-JONES), the singer/performer she sees as her idol. Despite a flourishing career with her sister, Velma ended up killing her and her husband, resulting in her incarceration. Fortunately for her, hotshot defense attorney Billy Flynn (RICHARD GERE) is representing her, and he's yet to lose a case.
Yet, when he meets Roxie, he decides to make her his star client since it will bring him better press through the likes of friendly journalist Mary Sunshine (CHRISTINE BARANSKI) and others. Soon, Roxie's a household name, resulting in Velma becoming jealous of this upstart and the attention she's receiving.
As a bandleader (TAYE DIGGS) introduces various musical numbers that symbolize plot developments, exposition and the characters' mindsets, and prosecutor Harrison (COLM FEORE) brings up Roxie's case, the two women repeatedly try to upstage the other and worry that new murderesses, such as Kitty (LUCY LIU), might steal their limelight.