A violent sociopath, he has committed several murders by the time he is sent to Oz to serve an 88-year sentence. Upon his arrival, Keller allies himself with the Aryan Brotherhood gang, "owing" the gang's leader, Vernon Schillinger, who protected him as a 17-year-old during a previous sentence, in exchange for sex. Schillinger arranges for the bisexual Keller to meet Tobias Beecher, Schillinger's former sex slave, with the intent of gaining his trust and seducing him. A mutual attraction instantly forms between them, and the two eventually exchange confessions of love. Unbeknown to Beecher, however, Keller has betrayed him to Schillinger and the Aryans, who beat him so mercilessly that they break both his arms and legs. Keller obviously enjoys the beating, but is briefly seen experiencing a moment of regret when he returns to his empty cell.
Keller later tries to seek Beecher's forgiveness, but Beecher rebuffs him, refusing to have anything further to do with him unless he confesses his role in the attack to prison authorities. Keller complies, but Beecher still rejects him. Keller begins attending counseling sessions with the prison psychiatrist, Sister Peter Marie "Sister Pete" Reimondo, as a ploy to win back Beecher's favor. During the meetings, Keller first tries to make her feel ineffective as a psychiatrist; then through various sexual provocations, forces her to question her commitments as a nun. When Sister Pete discovers that his confessions are insincere, she too turns her back on him.
Keller briefly allies himself with Ryan O'Reily for protection against the Aryans, who now hate him for becoming Beecher's lover and for turning himself in (as Beecher requested), implicating Schillinger. Combined, he and O'Reily, an inmate equally devoid of conscience, are a force to be reckoned with, plaguing Schillinger and, along with Beecher, playing a role in the death of his son, Andrew.
Keller eventually does get a chance at a kind of moral redemption when he saves Beecher's life after Schillinger stabs him and Beecher requests that Keller be moved back into their old familiar cell; they share a happy reunion on New Years' Eve.
Keller and Beecher's renewed relationship does not last in the face of Vern Schillinger's machinations. In the season premier, Keller was shot in the shoulder and Beecher pulls him to safety and his shooter kills two inmates and one guard, setting the alarm and his shooter kills himself. Unbeknown to Beecher, Schillinger contracts his son, Hank, to kidnap Beecher's children, Gary and Holly. Mad with fear and grief, Beecher believes false rumors claiming that Keller is responsible for the kidnappings. An attempt on Keller's life in retaliation ends their brief reunion, and the two spend the rest of the season attempting ways to hurt one another. Beecher delves into promiscuity, and Keller kills Beecher's lovers, including inmate Mondo Browne, to discredit the new manager of Em City, Martin Querns.
After killing Browne, Keller takes up with his former cellmate/lover, Ronald Barlog, to hurt Beecher. Barlog then secretly makes a deal with FBI Agent Pierce Taylor to give evidence against Keller and have him convicted of three murders in exchange for his own freedom. Beecher is immediately suspicious of Barlog and warns Keller, who dismisses the warning as mere jealousy. But Keller soon starts to have his own suspicions and eventually murders Barlog, snapping his neck while receiving oral sex from him. Just before killing Barlog, Keller confesses that he had indeed committed the murders the FBI suspected him of, and that his victims — all young, gay men — represented something within himself that he hated. When the police discover that Schillinger's other son, Hank, had been murdered and that the hit was ordered by an inmate from within Oz, Keller takes responsibility for the crime to protect Beecher and his family. He is then sent to Massachusetts to stand trial for this murder.
Keller is transferred back to Oz the following year, after Agent Taylor proves he lied about his involvement in Hank Schillinger's murder. He is then put in protective custody while the District Attorney's office tries to convict him of an unsolved murder (which he had indeed committed). While in protective custody, he begins an affair with one of the guards, Officer Claire Howell, but soon tires of her and begins rejecting her advances. Enraged, Howell brutally beats him, putting him in the infirmary, and tells her superiors that he attacked her. After he recuperates from his injuries, he is found guilty of the murder charge, and sentenced to death.
When Beecher is paroled, he shows his gratitude to Keller by helping him appeal his death sentence, which is subsequently overturned. At about this time, Beecher's father is stabbed to death in a suspiciously empty hall. While Keller's relationship with Beecher is by now somewhat estranged, he tries to show his former lover that he still cares by killing Franklin Winthrop, the inmate who had murdered Beecher's father to advance in the Aryan Brotherhood.
Keller then concocts a plan to ensure that he and Beecher can be together again; he asks Beecher to deliver a package of illegal medicine for his dying ex-wife. Beecher hesitates, but eventually agrees and takes the package. Shortly after Beecher leaves the room, Keller makes an anonymous telephone call to tip off the police, getting Beecher caught and sent back to Oz. Furious, Beecher rejects Keller once and for all. At this time, Beecher is offered a deal from the FBI to set Keller up and he seriously considers it. Meanwhile, Keller seems to get on friendly terms with Schillinger again.
A play of Macbeth is being put on by a number of prisoners with Schillinger in the lead role and Beecher as MacDuff. Keller takes a job backstage managing the props. He tells Schillinger that they will kill Beecher then later tells Beecher that he is being friends with Schillinger to keep Beecher alive. He then kisses Schillinger and tells him that he will switch Schillinger's prop knife with a real one so he can kill Beecher onstage. However, during the final fight scene, Keller switches Beecher's knife with a real one. Beecher stabs Schillinger unintentionally during a fight scene, thinking the knife in his hand is a prop. Keller claims to have no idea how a real knife got onto the set. Schillinger's death is considered an accident.
Afterward, Beecher returns to his cell, only to find that Keller is his new cellmate and discovers that Keller, despite their past, still believes they should be together. Keller reaffirms his love for Beecher and explains that he eliminated every obstacle between them, referring to Schillinger. He also claims to have taken care of the entire Aryan Brotherhood to keep Beecher safe from any retaliation. However, during a heated conversation Beecher demands to know whether Keller had set him up with the illegal drugs; when Keller admits the truth, Beecher rejects him for the final time. During the ensuing confrontation in EmCity Beecher pushes Keller away; Keller then leans forward towards Beecher, tells him he loves him and falls over a railing, while screaming "Beecher, don't!". The fall breaks his neck and kills him. Beecher is blamed for Keller's death and faces the death penalty.
At the same time, a package arrives from a friend of Keller's, containing an unknown contaminant. When opened by the Aryans in the mail room, the contents are released into the air, killing the inmates and two guards in the room and resulting in a total evacuation. In the final scenes, the entire prison is empty and several buses leave the premises loaded with prisoners and staff, and the camera focuses on Beecher, who can't help but smile knowing who was responsible.