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 West Virginia, Kimble arrives at a local coal mining town where he is roughed up by the redneck locals, and then chased by a sheriff's posse. Hiding in the mountains, Kimble meets Cassie, a young woman living in a remote cabin with her grandmother. Cassie tells Kimble she get him to safety because she knows the area, when she is really wanting to keep him around for her own selfish reasons. Meanwhile, Gerard flies to West Virginia after learning from the sheriff that Kimble has been spotted in the area and teams up with the posse to try to find Kimble.

While working as a gas station attendant in New Mexico, Kimble is taken hostage, along with customer Joanne, by two holdup men, named Miles and Vinnie. Once on the road, Kimble pretends that he is a criminal and is heading towards Los Angels for a ""big job."" At the same time, he lets Joanne know that he's on her side, but she's suspicious to his true motives. Once arriving in L.A., Kimble decides to set up Miles and Vinnie to be arrested. But Miles, not trusting Kimble enough, wants him to kill Joanne to prove himself.

After getting into a car accident in a rural Kentucky town, Kimble lands in jail by the redneck sheriff who hates outsiders. But Kimble manages to escape with his cellmate Davey ""Fatso"" Lambert. Hiding out at the Lambert ranch, Kimble sees that Davey's father and brother, Frank, treat the slow-witted Davey badly for blaming him for a barn fire years earlier. Kimble tries to prove Davey's innocence as Gerard flies out to Kentucky after learning of Kimble arrest and forms a posse to track him down.

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.

Kimble returns to his home town in Illinois after learning that his father, John Kimble, has suffered a heart attack and has donated his medical library to the University of Wisconsin and in the process of selling the family house. While Kimble hides out at the home of his sister Donna and her sympathetic husband Leonard, Kimble blames himself for his father's condition, but is more troubled by his younger brother Ray, whom belives Kimble is guilty and thinks he's to blame for ruining his life since people see Ray as ""the brother of a killer."" Meanwhile, Gerard arrives in town to search for Kimble and focuses on Donna and Leonard whom try to shake off the relentless detective long enough for Kimble to get out of town before Gerard finds him.

Herbie Grant, a second rate hoodlum, is shot in the leg while trying to rob a liquor store that Kimble works at. Herbie later takes Kimble hostage where Herbie claims that although he tried to rob the store, he is innocent of two other liquor store robberies in the other towns. Kimble agrees to help clear Herbie in which the hood lets the fugitive go. Kimble is summoned to the local police station to give his statement on the robbery where he is recognized by Herbie's sister, Lorna, whom works at the local post office. She threatens to turn Kimble in unless he turns over her brother whom she belives to be guilty of those other robberies. But at a local motel where Herbie is staying at, he is recognized by a maid who calls the police and they arrest him. Thinking that Kimble doublecrossed him, Herbie reports Kimble to the police.

While working as a health club masseuse, Kimble is recognized by Sheriff Bray, a local lawman with policial aspirations. But Kimble manages to escape with the help of co-worker Steve Edson. After confiding with Steve his secret, Kimble learns that Steve is a fugitive of conscience: five months earlier, Steve was tried and acquitted for the murder of his girlfriend Linda's abusive brother, a murder that Steve actually committed and he apparently cannot live with the guilt over having gotten away with it. Kimble reluctantly lets Steve travel with him. But Steve begins leaving behind clues that soon puts Sheriff Bray back on their trail, including contacting Linda for help and letting her vengeful other brother, Joey, track them down.

While working as a migrant worker in New Mexico, Kimble becomes an unwilling party to the kidnapping of a young boy whom is the son of his landowner boss. The boy, Jimmie, has been abducted by Ralph Simmons, a disgruntled former football player, along with his wife Helen and his cousin Dave. When Kimble discovers that Jimmie is a hemophiliac and that Ralph has bruised him during the abduction, Kimble must find a way to get the boy away from the kidnappers and to a hospital, or Jimmie will soon die from internal bleeding.

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.

Injuring after being shot during a police chase, Kimble seeks refuge at an orphange near a Navajo Indian reservation in Puma County, Arizona. Annie Johnson, the head teacher (and herself an orphan), removes the bullet and offers Kimble work as a teacher. Meanwhile, while the local sheriff Prycer belives that Kimble has escaped, a determined and overzealous deputy, named Steel, belives Kimble is still in the area and suspects Annie of sheltering the fugitive.

Kimble visits an enclosed plaza in the heart of the city. Due to a misunderstanding, on-site security mistakes him for someone else and gives chase. Thinking they are on to him, Richard tries to jump a fence but is caught by a guard, and has to punch him out to get away. A lady working at a camera store lets him stay at her place (in the plaza), while he rests and heals. To complicate things more, Kimble's earlier visit to the video store was caught on video tape, and someone who sees the tape recognizes him. Kimble's visit also coincides with an accidental shooting inside of a storage room, so the police are at the plaza, investigating.

Kimble, working as an apartment janitor in a nameless big city, becomes implicated in a murder when Roger Roland, a neighbor whom lives across the street, is a troubled young man and a part of Irish royalty, but he profanes his family history by dying his red hair black. Roger murders a neighbor woman in the building where Kimble lives by bludgeoning her to death with a marble statue after she refuses his advances. After a tenant reports seeing a figure run from the murder victim's apartment, the police arrive and suspect Kimble despite his alibi. Roger then hides the statue in Kimble's room and when Kimble finds it, he hides it in an air conditioning vent. Kimble thinks Roger is involved and tells his father, Edward, and Roger's younger sister Liz. But naturally, Edward Roland refuses to believe Kimble and unbelievably thinks Kimble is the killer and calls the police. Kimble escapes and tries, with Liz's help, to prove his innocence. Meanwhile, Gerard arrives in town after hearing the

Kimble finds work on Jake Lawrence's farm, where he develops a special friendship with Jake's autistic daughter, Cathy. But Kimble soon becomes nervous when the local sheriff, Mel Bailey, begins searching for Joe Burmas, a convicted murder having escaped from prison a few weeks before. Burmas attacks and nearly kills Kimble after trapping him inside a truck that crashes into a creek. Meanwhile, back in Stafford, Gerard has the local newspaper establish a $10,000 reward for Kimble's capture hoping someone will respond. A local storekeeper recognizes Kimble's face in the newspaper but decides to collect the money for himself. Kimble then tries to evade capture from a local posse, but he again runs into the murderous Burmas whom also takes Cathy hostage as well.

Kimble meets Willie Turner, a mentally disabled young man who is accused of hurting a child. Kimble reluctantly hides Willie at a carnival where Kimble now works. Kimble tries to persuade Willie to return to the hospital where his sister had him committed. But naturally, Willie is slow to understand what Kimble means and, on top of that, does not remember hitting the young boy he is accused of hurting. Willie's sister, Mary, as well as an attendant from the psycho ward at the local hospital, arrive searching for Willie and find him. But the attendant recognizes Kimble and calls the police. In trying to protect his new friend, Willie strikes the attendant, badly injuring him, and warns Kimble in which both men, now fugitives, take off in a stolen truck. Kimble hides out with Willie at a nearby auto wrecking lot, where he tries to persuade Willie to return to the hospital, while the sheriff and his men are already on their trail.

While working as a fishing crewman, Kimble becomes embroiled in a union strike which is orgainzed by Joe Donovan, the son of Kimble's employer, grizzled fisherman Tony Donovan. During a rally, Kimble, Tony and a few others are arrested. After being released, Kimble tries to leave town knowing his secret will be revealed, but he's prevented from doing so. When the police finally learn Kimble's idenity, they question Tony about his whereabouts, but the sympathic Tony claims not to know. He then offers to take Kimble to Mexico if he helps him out on his latest fishing trip. But Joe sees Tony smuggle Kimble on his boat and calls the authorities.

Kimble finds work at an upholstery store where the police are staking out the place in their search for an escaped killer, named Bowen. Kimble becomes aquainted with one worker, a Hungarian immigrant named Josef Karac, whom Kimble discovers that Josef is a doctor wanted by the police for an abortion that he performed years earlier. Meanwhile, the police stake out Dr. Karac's apartment where his wife, daughter and nephew live, while undercover cop, Jim Macklin, goes undercover as a worker at the shop where Bowen was last seen to investigate his girlfrend whom is Dr. Karac's daughter. But Macklin soon recongizes Kimble and begins a second investigation to try to capture him. In the meantime, Bowen returns and takes the Karac family hostage to force them to hide him from the police just next door.

Ralph Schuyler is a government agent who goes undercover as a boat captain to spy on Felice Greer, the wife of an international embezzler hiding out in Mexico and she's presumably coming down to him with the stolen money. Kimble happens to be on the boat too as a hired deck hand. When Ralph learns that Kimble's identity is false, he takes Kimble's fingerprints and after an 'emergency' landing, the agent leaves the fingerprints with a local Mexican shopkeeper and notifies the authorities of Felice's whereabouts. But when Ralph is badly burned in a engine room fire, Kimble tries to save him and takes over the boat's steering to safely make it to their destination. But when Kimble intercepts a cable with the incriminating report on his fingerprints, Kimble is torn between fleeing or staying to help Ralph, while Kimble also discovers that Felice's husband is up to no good concerning the stolen money.