In the film, he is a former Chicago Police officer turned security guard who has a prosthetic right arm and works for Devlin Mcgregor pharmaceuticals. He is sent by the Dr. Charles Nichols to murder Dr. Richard Kimble after Kimble discovers that the company's new drug, Provasic, was causing severe liver damage. He instead murders Kimble's wife. While on the run, Kimble eventually discovers his true identity as well as leading U.S Marshal Samuel Gerard to him, who becomes suspicious of Sykes and begins investigating him.
Later, Sykes corners Kimble on an El Train. At that moment, Kimble is simultaneously spotted by a civilian and a transit cop. Sykes kills the cop and tries to kill Kimble, but fails when Kimble is able to overpower him due to him only having one arm. He is then arrested, along with Nichols, while Kimble is driven off to be exonerated.