One night, Dr. Richard Kimble and his wife Helen have a heated argument over the idea of adopting children, since the couple cannot have any of their own. Richard storms out of the house and drives off. Later, he decides to return home and apologize.As Kimble drives up to the house, his headlights catch the figure of a one-armed man running from the house. Richard rushes inside and finds Helen dead, presumably the victim of a burglar she caught in the act. Richard is subsequently arrested and charged with his wife's murder.
Numerous attempts by police to find the mysterious one-armed man fail. A long courtroom trial ends and, based on circumstantial evidence, Richard Kimble is sentenced to death.
While enroute to the state penitentiary, the train on which Kimble is traveling derails, and Kimble escapes the bounds of Indiana Police Lieutenant Philip Gerard. Though free, Kimble is relentlessly pursued by Gerard, who is determined to apprehend his escaped prisoner. The series depicts Kimble's attempts to clear himself by finding the mysterious one-armed man while staying one step ahead of the law.