Dr. Richard Kimble, a respected Chicago vascular surgeon, arrives home one night to find his wife Helen brutally murdered. Despite his assertions of innocence, overwhelming circumstantial evidence points to him as the killer, including a 911 call Helen makes during the attack, in which she screams out her husband's name. Convicted of first-degree murder, Kimble is sentenced to death. While en route to prison, a catastrophic accident allows Kimble to escape. Now a fugitive from the law, he is determined to find his wife's true murderer and clear his name. His pursuit is relentless, leading him back to Chicago where he covertly investigates the crime amidst a manhunt led by the tenacious U.S. Marshal Samuel Gerard.

Marshal Gerard and his seasoned team launch an exhaustive search for Kimble, who narrowly evades capture while gathering clues about the one-armed man he claims is Helen's real killer. As Kimble delves deeper into his wife's death, he uncovers layers of medical and corporate intrigue that suggest a conspiracy involving prominent figures in the Chicago community. The chase becomes a high-stakes game of cat-and-mouse, with Kimble using his medical knowledge and survival skills to stay one step ahead of Gerard, whose dogged pursuit is both relentless and uncompromising. The tension escalates as Kimble pieces together the puzzle, inching closer to the truth while the gap between the fugitive and the law steadily narrows.