This is a list of characters in the American television series Prison Break. The characters are listed alphabetically by their last name or by the name which appears in the episode credits.

Lincoln Burrows (played by Dominic Purcell) is falsely convicted of the murder of Terrence Steadman and sentenced to death for the crime. He is surprised to see his younger brother Michael Scofield in the same prison and who is planning to break him out of prison before his execution. He evaded authorities after escaping from prison and has been exonerated of all charges. In the second season of the series, the story continues to follow Lincoln, his brother and other escapees as they try to evade the authorities pursuing them. Away from the prison setting, Michael and Lincoln are frequently featured in scenes together in the first seven episodes. When they fail to retrieve L. J. Burrows before his trial, they decide to head to Utah to find Westmoreland's hidden money. In season 3 he is free and successfully assists Michael and James Whistler to break out of Sona. As of season 4, he is now part of Self's covert "A-Team" assembled to bring down The Company. He is also in the very last scene when he visits Michael Scofield's (his brother) grave, and he puts an origami crane on top of the grave so he can remember the time when he made them for him, so he would always know that his brother was caring for him. In season 5, he finds out Michael is still alive and incarcerated in Yemen, and leads an operation to save his brother.

Purcell was cast three days before the start of production and consequently, he was the last actor to join the original cast. He auditioned for the role while he had a recurring role as Tommy Ravetto on North Shore.

Michael J. Scofield (played by Wentworth Miller) is the protagonist of the series and younger brother of Lincoln Burrows. He designs an elaborate escape plan and tattoos it to his body to free his older brother who has been framed for murder and sentenced to death via the electric chair. He successfully executes this plan, freeing himself, Lincoln and 6 other convicts, but ultimately fails to evade the police in Panama. In the second season of the series, the story continues to follow Michael, his brother and other escapees as they try to evade the authorities pursuing them. Away from the prison setting, Michael and Lincoln are frequently featured in scenes together in the first seven episodes. When they fail to retrieve L. J. Burrows before his trial, they decide to head to Utah to find Westmoreland's hidden money. Michael and Lincoln travel together, after the fugitives separate to accomplish each of their individual goals. Season 3 is centered around Michael breaking out of prison again, however, this time from the self-governed prison of Sona, situated in Panama. In season 4, he reunites with Sara after discovering her death in season 3 was faked, and she is part of Agent Donald Self's covert "A-Team", which is assembled to bring down The Company. Michael has low latent inhibition, a personality trait which allows him to notice things that others would not. This, along with his genius-level intellect, is what enabled him to break out of both prisons. He also suffers from a tumor of the hypothalamus, which causes nosebleeds, disorientation, and extreme pain. In season 5, he is revealed to be incarcerated in Yemen under a different name; Kaniel Outis. It is gradually revealed that Michael, along with a fellow prisoner named Whip, are undercover CIA operatives, but were betrayed by a mastermind agent known as Poseidon.

Veronica Donovan (played by Robin Tunney; seasons 1–2) is a real-estate lawyer and a longtime friend of the protagonists of the series, who unsuccessfully tries to find evidence to exonerate Lincoln Burrows. She serves as the primary ally of the brothers in the show's first season. Veronica had a relationship with Lincoln in High School and the two also dated each other after she graduated from Baylor law school. However, at the start of the show they have broken up since several years. When Lincoln is first framed for the murder of Terrence Steadman, Veronica assumes that he is guilty and moves on with her life. Sometime between the episode "Brother's Keeper", and the pilot, she gets engaged to Sebastian Balfour. Although she is a real estate lawyer and not a criminal lawyer, Veronica defends her childhood friend, Michael Scofield at his trial. Initially, she doesn't believe Lincoln's innocence and is convinced by the security tape footage. However, after the disappearance of Leticia Barris, a witness who could prove Lincoln's innocence and the death of a bishop who opposed Lincoln's death penalty, Veronica is led to believe that Lincoln might have been set up. Thus, Michael's arrest causes her to grow more involved with Lincoln's case, straining her relationship with Sebastian. Following the disappearance of Leticia in the episode "Cell Test", Veronica decides to postpone the wedding as she claims that she cannot focus on it at the time. Sebastian is hurt by this and breaks off the engagement.

She approaches Project Justice for help with Lincoln's case, knowing that she herself doesn't have any experience in death penalty cases. However, they refuse to partake in her case. Nick Savrinn later offers his help after telling her that his father was similarly accused of a crime he did not commit. Together, they work tirelessly, trying to uncover the truth behind Terrence Steadman's apparent murder. The original security tape which they were looking for is destroyed and in the subsequent episode, "Riots, Drills and the Devil Part 2", they are threatened via a public phone call in Washington, D.C. and are targeted by Paul Kellerman and Daniel Hale, who are members of the conspiracy. They were nearly killed by an explosion in Veronica's apartment and in the following episodes, LJ Burrows joins both of them after escaping from the agent's clutches. All three of them go into hiding. Their lives are once again in danger when an assassin called Agent Quinn manages to find out their secret location. Veronica eventually manages to knock him unconscious and escape with LJ and a wounded Nick. Veronica is then contacted by a secret informant, who claims to be willing to provide information. Knowing that hiding is not the answer, Veronica decides to go out into the open and reveal the conspiracy to the public. Veronica meets with the informant, agent Hale, the following night, where he reveals that Steadman is still alive. Hale is executed by Kellerman before he can provide proof, and Veronica barely has time to hide shortly before Kellerman arrives.

Now left more or less empty handed, Veronica and Nick nevertheless goes back to the court on Lincoln's execution day for one last time to appeal for Lincoln's case, but this ultimately fails as the judge rules against them. Fortunately, someone slips in evidence in the last minute which helps to stall Lincoln's execution. Veronica and Nick decide to send someone to do a test on Steadman's body, but the dental records matched Steadman's records. Following this, she decides to find out where the real Steadman is hiding. In "J-Cat", Nick, Veronica and L. J. return to New Glarus to visit the dead Quinn, where they obtain his cell phone. Eventually, they found out Terrence Steadman's hideout in Blackfoot, Montana. However, at the end of the episode "Tonight", Veronica is betrayed by Nick, who turned out to have made a deal with John Abruzzi to have her "ready and waiting" at the airport on the night of the escape in exchange for his father's freedom. Nick is conflicted, however, and ultimately lets her go to the airport as he doesn't want Veronica to be killed. Now alone, she travels to Blackfoot, Montana and manages to sneak into Steadman's house and confront him face to face.

In season 2, following her confrontation with Steadman (Jeff Perry), Veronica is executed in cold blood by secret service agents ordered to ensure that Terrence Steadman is kept hidden. Veronica is the first main character to be killed off in the series.