When the protagonist of the series, Michael Scofield (Wentworth Miller), successfully orchestrates the escape of eight prisoners from Fox River State Penitentiary, Mahone is assigned to spearhead the task force assembled to recapture the fugitives and manages to capture four of them. However, he is arrested in Panama and imprisoned in Penitenciaría Federal de Sona in the second-season finale. Mahone manages to escape, and is coerced into taking down the Company, a secret group of multinationals which exerts an influence on the White House. An assassin is hired by the Company to murder his son, and Mahone spends the majority of season four seeking revenge.
The writers created Mahone's character in the second season so that there would be a fugitive pursuer who was not corrupt. When the writers saw that the number of antagonists was increasing, they decided to make him the alter ego of Scofield. The writers try to let Mahone inhabit a gray area, shifting the audience's sympathy for the character. Fichtner, attracted to the potential of the character, was cast as Mahone just one day before filming began for the second season; he signed on for only two seasons, but was convinced to appear in a third.
Mahone is born in Boardman Ohio into an abusive family, and repeatedly beaten by his father. After joining the military Mahone is transferred to Special Ops during the Gulf War, later becoming an FBI agent. The nature of his quick advancement is questioned, and many of his files are classified.
He marries a woman named Pamela (Callie Thorne) and they have a son, Cameron. The marriage lasts for 12 years until Mahone abruptly ends it without explanation, ordering his family out of the house.
Before separating from his wife Mahone pursues Oscar Shales, a murderer whom he struggles to capture; it is revealed that Mahone killed Shales and buried the body in his backyard. Fearful that his wife would discover his secret, he cuts her out of his life. Mahone is plagued with visions of Shales, which cause him to self-medicate with prescription drugs.
After eight prisoners escape from the Fox River State Penitentiary, Mahone leads the investigation to capture them. Reviewing their files, he decides to concentrate his efforts on Michael Scofield, mastermind of the breakout. He tracks the escapees to Oswego, Illinois, but they manage to escape. Mahone continues to pursue Michael and his brother Lincoln Burrows (Dominic Purcell), who are able to avoid him on several occasions. While investigating a car explosion Mahone is shown to have a drug problem, swallowing pills concealed in a pen. Mahone eventually tracks down John Abruzzi (Peter Stormare) and David "Tweener" Apolskis (Lane Garrison). Mahone orders his men to shoot Abruzzi to death when he fails to surrender, and later murders Tweener in cold blood. When he returns to his office, Mahone is questioned by Internal Affairs Agent Richard Sullins (Kim Coates) about their suspicious deaths.
It is revealed that Mahone is being blackmailed by Paul Kellerman (Paul Adelstein), a Secret Service agent forced to work for the Company. Kellerman threatens to reveal that Mahone killed Shales, and forces him to kill all the escapees in exchange for his silence. Although hesitant, Mahone agrees when an operative of the Company, Agent Kim (Reggie Lee), threatens to murder his family.[[|]] Mahone continues his hunt for the remaining six escapees but is betrayed and shot by Kellerman, who transfers his allegiance to the brothers. He survives and decides to stop chasing the escapees, but is forced to resume his search when his son is injured in a car accident orchestrated by one of Kim's agents. Before returning to work, he murders the agent who arranged the accident.[[|]] Mahone returns to his FBI field office, where he is informed by Agent Wheeler (Jason Davis) that Internal Affairs is investigating him.
When Charles "Haywire" Patoshik (Silas Weir Mitchell) murders a civilian, Mahone asks Brad Bellick (Wade Williams) (former captain of correctional officers at Fox River) to help him find Haywire. Bellick finds Haywire, chasing him up a grain mill; Mahone climbs the mill and talks Haywire into committing suicide.
Mahone's next target, Benjamin Miles "C-Note" Franklin (Rockmond Dunbar), narrowly evades him; C-Note soon offers to turn himself in, however, if his wife and child are cared for. C-Note is taken to jail, and Mahone tells him to commit suicide in order to guarantee the protection of his family. C-Note attempts suicide, but is rescued by the guards. Sullins makes a deal with him, and promises to release him if he testifies against Mahone.
Because he is unable to capture Michael, Mahone orders Agent Lang (Barbara Eve Harris) to follow Michael's girlfriend Sara Tancredi (Sarah Wayne Callies). Mahone's sanity begins to unravel from his determination to catch Michael and Lincoln, and from his benzodiazepine addiction. Michael and Lincoln travel to Panama, where Mahone lures them into a trap by impersonating fellow escapee Fernando Sucre (Amaury Nolasco). He captures Lincoln and contacts Michael, ordering him to surrender Charles Westmoreland's (Muse Watson) five million dollars and his boat, the Christina Rose. Michael plants drugs on the Christina Rose, which he gives to Mahone. After an attempt to kill Kim, Mahone takes the boat and leaves; however, he is arrested on drug-possession charges. Mahone is taken to Sona along with Michael, Bellick and Fox River escapee Theodore "T-Bag" Bagwell (Robert Knepper).
Inside Sona, Mahone attempts to convince Michael to form a partnership. Michael refuses to work with him, angry because Mahone killed his father. As new prisoners, Michael and Mahone are brought before Lechero (Robert Wisdom) (a prisoner who rules Sona and its residents). When Mahone learns about the bounty placed on fellow inmate James Whistler (Chris Vance), he manages to find him and deliver him to Lechero.
Mahone begins to suffer from drug withdrawal and is informed by his state-appointed lawyer that his trial is almost a full year away. When Whistler realizes that Michael is not entirely on his side, he forms an alliance with Mahone. Mahone deduces that Michael is planning to break Whistler out of the prison, and Michael eventually agrees to let him join the escape. After he begins hallucinating about Haywire, Mahone accepts heroin from T-Bag to calm himself.
Agent Lang visits Mahone and offers him a deal: eight years in a St. Louis prison in exchange for testifying against the government in the Lincoln Burrows conspiracy, or multiple homicide charges if he does not cooperate. Mahone eventually accepts the offer and confesses to Lang that he killed Shales, and that guilt made him turn to drugs. Because he is unable to maintain his composure while testifying, Mahone's testimony is dismissed, and Lang is forced to return Mahone to Sona.
Mahone (now rehabilitated) approaches Whistler and Michael and rejoins the escape. He is informed that their escape route (a tunnel leading to the edge of the prison) is almost complete, and that they will break out of Sona that night. Michael, Whistler, Mahone and fellow inmate McGrady (Carlo Alban) manage to escape; Lechero, T-Bag and Bellick are caught by the Sona guards.
Lincoln wants to shoot Mahone in revenge for killing his father, but Whistler escapes from Lincoln's custody and Lincoln is forced to chase him. Mahone takes advantage of the situation and flees, eventually making his way to a bar.
Mahone is approached by Whistler, who offers him a job in the Company with him and operative Gretchen Morgan (Jodi Lyn O'Keefe). Mahone warns Whistler that Gretchen is the "weak link", and that Michael will eventually hunt them down if Gretchen has indeed killed Sara.
Mahone accepts Whistler's offer to work for the Company. However, the group is secretly working with Homeland Security to destroy the Company, focusing their attention on a card (code-named "Scylla"), which contains information on all of the Company's agents and operations. Whistler finds the card; however, he is killed by the Company's hitman, Wyatt (Cress Williams), who takes the card.
Mahone returns to his family home to find his son has been murdered and since he is a wanted criminal, he is arrested by the police. Mahone is contacted by Agent Don Self (Michael Rapaport), a Homeland Security agent who was working with Whistler to take down the Company. He offers Mahone freedom if he joins an unofficial operation to recover Scylla from the Company. Mahone accepts, learning that other members of the operation are Michael, Lincoln, Sara, Bellick, Sucre and computer hacker and identity thief Roland Glenn (James Hiroyuki Liao). The group devises a plan to regain the card, which succeeds. However, they learn that Scylla is actually made up of six cards held by different members of the Company. The group continues to look for the other cards, while Mahone asks Lang to find out who killed his son.
Mahone obtains a picture of Wyatt and meets with his estranged wife Pam, who makes him promise to hunt down and kill Wyatt. When Wyatt is captured Mahone tortures him, forcing him to apologize to his wife over the phone. He ties a cinderblock to Wyatt's wrists, and drowns him in the ocean. The group manages to complete Scylla, and Lincoln absolves Mahone for his role in his father's death. However, Self betrays the team and steals Scylla, forcing them to be fugitives once again.
While the others hunt Self, Mahone meets with Lang and asks for help. Lang calls Wheeler to help Mahone; however, Wheeler lies to Mahone about a meeting with the Attorney General and arrests him. While transporting Mahone to the airport, Lang allows him to escape and lies to Wheeler about the direction in which he has fled. Mahone returns to help Lincoln, Self, T-Bag and Gretchen retrieve Scylla. When Gretchen is shot while trying to double-cross the team, Mahone and the others leave her for the authorities.
After realizing Lincoln's mother (Christina Scofield) took Scylla, Mahone helps him stop her and retrieve Scylla after the Company threatens him with a photo of Pam. He later saves Lincoln from being assassinated by one of Christina's snipers. Mahone identifies one of the people who has connections with Christina, Vincent Sandinsky. However, the team does not find any connections with him and he believes his story (which is a lie). They catch him in the lie; after Krantz arrives to take charge they interrogate Sandinsky, who reveals some information about a hotel room. He and the team track a car rental slip and after more digging, eventually find the car (with their passports) outside the energy conference; they realize it is a set-up. It is revealed that Christina is setting the team up for the assassination of the Indian Prime Minister's son (who was thought to have brought Scylla). After the assassination of Naveen Banarjee, Mahone and Self are outside the hotel on the phone with Scofield and Burrows. The brothers tell Mahone to go the apartment where Sara is holding Christina hostage, and make Christina talk by any means necessary. Mahone goes to the apartment, finding only Sara tied up; he unties Sara and heads back to the loft, where the General and T-Bag are. Mahone, Michael and Lincoln then head to a bank, where they believe Christina is with Scylla. They enter the bank wearing masks, to avoid being recognized. They take Scylla, and when they get outside a shootout begins. Mahone and Michael get away, but Linc is caught. In the next episode, Mahone and Michael are the only ones left on the team. Linc and Sara are captured, and Self is in the hospital. Mahone and Michael decide it is time to bring the Company down and save everyone; they decide to go after Lincoln first. They set up a trap for Christina, but the police arrive; one of Christina's guards is killed in an explosion set up by Michael and meant for Christina. Later Michael gives Scylla to Mahone without the hard drive and has him save Lincoln, while Michael goes after Sara. Mahone has a bomb in Scylla which is large enough to kill Christina and her man, Downey. Christina has Mahone put in the same room Lincoln is in, moving Lincoln to the other side of the room. When the bomb fails to detonate and Christina realizes there is something wrong with Scylla, she calls on Mahone to check the device and threatens to kill him if he cannot activate it. He sets it manually. After a struggle with Christina and Downey, Mahone runs to the room where Lincoln is; the bomb detonates, killing Downey and (apparently) Christina. However, she survives. Michael and Sara come to pick up Lincoln and Mahone and head to another location, where Scylla's hard drive is. The remaining team then heads to a hospital for supplies to treat Lincoln's gunshot wound. Sara and Mahone go into the hospital, and Mahone is arrested by Federal agents. He is later freed and exonerated when Michael delivers Scylla to Kellerman. In the series' epilogue (set four years later), Mahone, Lincoln, Sucre, Michael's child and Sara visit Michael’s grave at a beach.