Richard Kimble rides into Tucson, Arizona under the name James Lincoln. He checks into a hotel and finds a job as a bartender at the Branding Iron. He meets Monica Welles (Vera Miles), the piano player who escaped from her stalking jealous husband (Ed Welles) played by Brian Keith.

In San Francisco, Kimble is nearly run over by a car driven by Ruth Norton, a young flight attendent distraught over discovering that the man she has been dating for the past four months is married with two children. While recuperating in the hospital, a delirious Kimble flashes back to the months leading upto the night of Helen Kimble's murder and Kimble first seeing the one-armed man fleeing from his house. Followed by Kimble's trial, sentence, and escape from the train wreck. Ruth, who has been keeping a vigil at Kimble's bedside, hears him mutter Helen's name. Thinking that he's in some kind of trouble, Ruth takes Kimble (now going by the alias George Browning) to her apartment to recover. Kimble then gives Ruth advice on her relationship with her boyfriend, Paul, and to put her life problems in perspective.

A discarded photograph, with Kimble in the background, leads Gerard to Chicago where he assembles a team of detectives where they trap Kimble within an eight-block radius of the city. With Kimble wondering from place to place, and being recognized by whomever he comes into contact with, he flees from both policemen and local citizens, finding refuge in a small house which is the home of two middle-aged men, named Jake Devlin and Sam Reed, whom have long argued over his innocence.