It was later followed by a 1998 spin-off, U.S. Marshals.
Dr. Richard Kimble is a prominent Chicago vascular surgeon. He arrives home one night to find his wife Helen fatally wounded by a one-armed man. Kimble struggles with the killer after that, and arms his prosthetic arm. but the assailant escapes. The lack of evidence of a break-in, his being the beneficiary of Helen's lucrative life insurance, and a misunderstood 9-1-1 call, result in his conviction of first degree murder and a death sentence because of it. On his way to death row aboard a bus, his fellow prisoners attempt an escape. The pandemonium results in a number of dead and wounded, causing the bus to fall down a ravine and into the path of an oncoming train. Kimble escapes the destructive collision and flees the scene in the nick of time. Deputy U.S. Marshal Samuel Gerard and his colleagues Renfro, Biggs, Newman and Poole, arrive at the crash site and formulate a search plan to apprehend the escaped convicts. Kimble sneaks into a hospital to treat his wounds and alter his appearance. He eludes the authorities and makes a getaway. Kimble is eventually cornered by Gerard at the leading edge of a storm drain flowing into a dam. Kimble leaps from the viaduct into the raging water, narrowly survives and escapes.
Kimble returns to Chicago to hunt for the murderer and acquires some money from his friend and colleague Dr. Charles Nichols. Posing as a janitor, Kimble enters Cook County Hospital's prosthetic department to obtain a list of people who had their prosthetic arm repaired shortly after his wife's murder. Following a police lead confirming Kimble's recent whereabouts, Gerard speculates that Kimble must be looking for the one-armed man.
Later, Kimble breaks into the residence of one of the people on the list; a former police officer named Fredrick Sykes. Not only does Kimble confirm that Sykes is the murderer, but he also discovers that Sykes is employed by a pharmaceutical company, Devlin MacGregor, which is scheduled to release a new drug called Provasic. Kimble had investigated the drug in the past and revealed that it caused liver damage, which would have prevented it from being approved by the FDA. He also deduces that Nichols, who is leading the drug's development, arranged a cover-up and ordered Sykes to kill him; his wife's death was incidental. Gerard follows Kimble's lead to Sykes' home, whose existence was known to the Chicago Police Department but withheld from the defence, and, after realising that Sykes is lying, he draws the same conclusion after looking into the files in the case again and by continuing to follow Kimble´s lead.
As Kimble takes an elevated train to confront Nichols at the drug's presentation in a hotel, Sykes appears and attacks him. In the ensuing struggle, Sykes shoots a transit cop before being subdued, handcuffed and knocked out to a pole by Kimble. Kimble arrives at the pharmacon conference and interrupts Nichols's speech, accusing him of falsifying his medical research and orchestrating his wife's consequent murder and the following murder of Lance a few months later, a colleague who also worked in the investigation and also realised the correctness of Kimble´s investigation.
They begin to fight while being chased by the marshals and police. Kimble, Nichols, Renfro and Gerard find themselves in the hotel's laundry room. Gerard calls out to Kimble and says that he is aware of the conspiracy fabricated by Nichols by disclosing to him, that Nichols had, as the files showed, his car that night and the keys for his house and that he called Sykes on his phone to inform he had the keys, so that he could enter the house without a sign of a break-in. Hearing this, Nichols knocks out Renfro and takes his gun. Nichols then attempts to shoot Gerard, but Kimble attacks him from behind, rendering him unconscious. Kimble surrenders to Gerard, who escorts him out of the hotel.
Nichols and Sykes are arrested, while Kimble is exonerated and driven away from the crime scene by Gerard. In the meantime the press gathers at the scene and investigates the new revelations putting the Chicago Police Department on the defensive on the way.
- Harrison Ford as Dr. Richard Kimble
- Tommy Lee Jones as Deputy U.S. Marshal Samuel Gerard
- Sela Ward as Helen Kimble
- Joe Pantoliano as Deputy U.S. Marshal Cosmo Renfro
- Andreas Katsulas as Fredrick Sykes
- Jeroen Krabbé as Dr. Charles Nichols
- Daniel Roebuck as Deputy U.S. Marshal Robert Biggs
- Tom Wood as Deputy U.S. Marshal Noah Newman
- L. Scott Caldwell as Deputy U.S. Marshal Erin Poole
- Julianne Moore as Dr. Anne Eastman
- Ron Dean as Detective Kelly
- Joseph Kosala as Detective Rosetti
- Jane Lynch as Dr. Kathy Wahlund