John Abruzzi held the title of the mob boss in the feared Chicago Mafia before he was incarcerated. He is convicted and sentenced based on the witness testimony of Otto Fibonacci who saw Abruzzi order another mobster to shoot and kill two men. Abruzzi ordered a hit on Fibonacci, who was entered into the witness protection program by the government, while Abruzzi was sentenced to 120 years without parole.
As a former Chicago mob boss, Abruzzi enjoyed celebrity status amongst the prisoner population at Fox River. He ran Prison Industry (PI), an internal work program for the convicts, and was both highly respected and feared by the rest of the cons inside Fox River's walls, and his inmate number is 81004. His mobster status also allowed him to enjoy a certain extent of autonomy and freedom inside the prison's walls, especially from the head of the internal correctional officers Captain Brad Bellick, who was on the payroll of Abruzzi's associates. Abruzzi proved that he would go to great lengths to find Fibonacci, even cutting two of Michael Scofield's toes off trying to extract Fibonacci's location from him. Abruzzi has also been known to have attempted to stop T-bag from having a sexual and violent interest in Scofield and Burrows. Eventually Abruzzi realized that Michael was not going to be easy to crack, so he decided to keep his enemy close and teamed up with Michael to break out of prison.
When T-Bag told his cousin James about the break out plan, Abruzzi ordered one of his men on the outside to make James disappear for a week. The kidnapping went bad, resulting in the death of both James and his son, who was, apparently, being used as a human shield. Abruzzi, despite being deeply saddened, had his men inside of the prison rough T-Bag up. Badly injured and fearing for his life, T-Bag finally agreed to back out of the escape plan. Abruzzi, recently finding religion as an outlet for his pain, decided not to kill him, this proved to be a big mistake, as T-Bag immediately took the opportunity to slash Abruzzi's throat.
Abruzzi was evacuated from Fox River by helicopter to receive treatment for his injuries. This complicates Michael's escape plan, as a plane Abruzzi owned was the planned getaway vehicle. Abruzzi however survived and rejoined the escape attempt, apparently a changed man. He later escaped with Michael, Lincoln Burrows and other inmates. During the escape, T-Bag handcuffed himself to Michael. However, Abruzzi used an axe to cut off T-Bag's hand, simultaneously taking his vengeance and ridding the group of T-Bag. Abruzzi was one of the group of five who was forced to run on foot after the plane left them behind.
On the morning after the escape, John Abruzzi found himself with his fugitive comrades, continuing to evade the authorities on foot. After narrowly passing a freight train to create more distance between them and the authorities, the group of five fugitives were trapped by an armed hunter who is aware of their fugitive status. Abruzzi quickly took matters into his hands by taking the hunter's daughter hostage. As the hunter lowers his weapon, they capture his SUV and continue to Oswego to find Michael's hidden cache in the cemetery where they all found a change of clothing. The fugitives went their separate ways soon after this.
Abruzzi met up with his family and together they planned to catch a cargo ship to Sardinia. Before he and his family could leave, however, Abruzzi is informed that Otto Fibonacci is staying at a motel outside of Washington D.C.. Abruzzi at first questions this but proceeds when the source is confirmed regardless of his wife's pleas. However, it turned out to be a trap set up by Agent Mahone and the FBI in an attempt to recapture him. Brazenly, Abruzzi walks out of the motel room with a gun in hand. Mahone states that Abruzzi must put the weapon down, stating that the men beside him are 'serious guys', and that they have instruction to shoot at the first sign of agression. Mahone exclaims "You're going back to Fox River today, or the morgue. That's your call. Put your hands behind your head and kneel." Abruzzi looks at him and scans the area before saying his final words, "I kneel only to God. I don't see him here."
Just as Abruzzi raises his gun in his final-stand, Mahone takes cover and watches on as the FBI team riddles Abruzzi with bullets, killing him.