Lydia Thorne is a wealthy flapper who lives a life of wild abandon. Despite her carefree ways, she is loved by moralistic district attorney Dan O'Bannon. After a night of wild partying, she causes the death of a police officer in an automobile accident. Despite his feelings, Dan is forced to prosecute her and sends the spoiled socialite to prison. While incarcerated, she learns the value of hard work and cooperation, and leaves her former life behind forever. Dan, however, is wracked with guilt over what he has done to the woman he loves, and falls into a life of alcoholism. Upon her release from prison, Lydia discovers that the former crusading D.A. is now a homeless vagrant. She vows to bring Dan back from the brink, but it may be too late.

Manslaughter is director Cecil B. DeMIlle's statement on the loose morals of the Roaring Twenties. At DeMille's insistence, screenwriter Jeanie Macpherson had herself jailed for stealing a fur coat so the film's depiction of a women's prison would be accurate (she was released after the police discovered the motivation behind her thievery.) After his cycle of films starring Gloria Swanson ended with The Affairs of Anatol (1921), Leatrice Joy had become DeMille's preferred leading lady. She was nearly injured during the film's car chase sequence, which incorporated crude special effects accomplished by fitting her car with a platform that could also hold the director and two cameramen. A scene that depicts a Jazz Age party as a Roman orgy is just as shocking today as it was in 1922, and prefigures DeMille's later historical epics. In fact, Manslaughter would be one of the last of DeMille's "social problem" pictures. He would make his first version of The Ten Commandments the following year, which would also star Joy. The film also features what is widely considered the first onscreen same-sex kiss of a romantic nature during a scene set in the women's prison.