When mobsters kill the witness he was assigned to protect, a dedicated policeman investigates the case on his own.

Chicago hoodlum Johnny Ross defrauds his Mafia associates and escapes to San Francisco where he agrees to testify before a Senate subcommittee on crime headed by ambitious politician Walter Chalmers. At the request of Chalmers, Det. Lieut. Frank Bullitt is assigned to protect Ross who is hiding out in a dilapidated hotel; two gunmen manage to enter Ross's room, however, and seriously wound him. Chalmers then warns Bullitt that he will destroy his career if Ross dies. When Ross is stabbed to death in the hospital, Bullitt persuades a member of the hospital staff, Dr. Willard, to help conceal the death, and he sets out to investigate the case. The Mafia gangsters follow him, but Bullitt escapes in an automobile chase through San Francisco that ends when the Mafia car crashes into a gasoline pump and explodes. Despite the objections of his girl friend Cathy, Bullitt retraces Ross's movements and eventually learns that the dead man was a decoy, and that the real Ross plans to leave the country under the name of Albert Renick. Tracing a phone call Ross had made to a San Mateo motel, Bullitt drives there with Cathy and finds a murdered woman with $30,000 in traveler's checks made out to Albert and Dorothy Renick. Bullitt then learns that Ross has booked a seat on a night plane to London. He races to stop him at the airport, but runs into Chalmers, who admits that he sent him to guard the wrong man and demands that the real Ross be taken alive. After an angry exchange with Chalmers, Bullitt goes after Ross, chases him from a departing plane onto the runway, and finally kills him as he tries to escape.