Michael is once again imprisoned, but now in SONA (Panama), together with T-Bag, Mahone and Bellick. The prison is solely ruled by inmates, whose local prison-lord Lechero feels threatened by Scofield's 'fame'. Lincoln tries legal means to get Michael transferred, and gets a call from a relative. Both receive the same message, through different channels, from The Company.

After Michael gets bad news from Lincoln, he sets out to find a prisoner named James Whistler, who holds the key to his freedom. That's easier said than done: James Whistler is hiding in Sona because there's a price on his head, and Lechero is not about to help Michael find him. In addition, both Mahone and Bellick want to get to Whistler too. Meanwhile, T-Bag won't allow a little humiliation stop him from insinuating himself into Lechero's good graces.

Lincoln tries to save LJ and Sara. But he can't. Meanwhile, Michael has a phone conversation with Sara. And Lincoln gets a call from Susan B. saying that she put something in the garage for him.

Aftermath of Sara's death, Lincoln decides not to tell about it to Michael. Susan B. told Lincoln that if he does something wrong again, she's going to send pieces from LJ to him. Meanwhile, Sucre got a job in Sona. And Sofia starts to help Linc.

A test with a rat proves the tower snipers are very good, so Michael figures the only option to breaking Whistler out within 24 hours has to be at 3 PM, during the distraction of soccer game. Sucre accepts $5,000 from Lechero's cousin, Augusto, to smuggle a package into Sona. Linc is to arrange transport outside, but he and Sofia get turned away roughly by an army patrol two miles away. He tells her Sara has already been killed. He keeps it from Michael, as LJ is his ultimate priority. New prisoner Andrew Tyge is robbed to his boxers on arrival, and recognizes Whistler (who denies it), mentioning the McFadden, Nice in 1997. He is warned off by Mahone who has noticed Tyge snooping around Michael and Whistler. They plan an electric signal disturbance device to distract the guard tower. Before they can make a move, a reflection from the binoculars is spotted: the troops move in and find it in his cell. Michael admits it's his. When the commander is about to shoot him, Whistler claims it's his for bird-watching, and proves it showing the ornithology book (the one Linc couldn't hold on to).

Tyge tells Michael that he and Whistler were co-employees at the McFadden, a hotel in Nice, France. Mahone worries about Tyge's constant, keen observance of Whistler. Having to re-plan hastily, Michael tells Linc to find out the location of the nearby cafe and drug the guard's coffee, and also demands pictures of LJ and Sara before he escapes. Tyge is stabbed to death. Lechero questions McGrady and has Whistler dragged away for a confession. Michael believes Mahone and Bellick's denials. T-Bag offers Michael a ring he stole from Sammy (his rival for Lechero's confidence), to use to frame Sammy for Tyge's stabbing. Michael finds the murder knife under Mahone's bed and goes to Lechero to denounce Mahone, only to find he has just walked out of the prison. Agents Richard Sullins and Felicia Lang arrive at Sona to present Mahone with a plea bargain from the US Justice: a term reduction to 8 years for testimony against the government conspiracy and Lincoln. He could be out in 4 years, but Mahone refuses, now he faces life imprisonment. Lechero administers justice for Tyge his own way. Linc and Sofia succeed in drugging Captain Hurtado, but Susan finds out the brothers had a different timing planned and threatens LJ's life. With no recent pictures available, Linc confesses Sara's death, causing Michael to make a drastic decision.

Mahone is assured all he has to do is tell the truth, enjoying full immunity. Michael tells Whistler their row is part of a diversion, the escape is now or never, before the drug in the guard's coffee wears off. Just when the critical sun reflection blinds the other tower guard, they must wait and hide till Sammy has passed, but get through the cut bars. They climb down, but the glare disappears so they must climb back up as there is not enough time to escape. They get back in time and out to the courtyard, but Lechero refuses to allow them to cancel their duel to the death in the courtyard, which had been intended as a fake diversion. Sofia draws a gun on Lincoln to prevent him from turning Whistler over to killers. He retorts that's condemning an innocent L.J. to death. Guards wake the passed-out Captain Hurtado, see the climbing rope and storm into the prison. The Colonel shoots Papo, one of Lechero's crew, 'for not telling' and exposes his deal with Lechero, questioning if he's the right man for the job. Hearing the Sona siren, Linc flees by car and when Susan calls, he lies, telling her he has the 'escapees' in the trunk, but Pike, another company operative phones her: the roll-count was complete. Sucre stops her van by crashing into it, but even when Linc holds her at gun-point her accomplice won't trade L.J. He releases her and gets a short extension to find out what happened. Failing a hearing, Malone now believes Justice official Richard Sullins is setting him up to confess. Michael is dragged before Lechero, but not to be punished, he's ordered to take the fallen boss along when he and Whistler escape. Susan asks instructions from Whistler, he tells her - as Gretchen - to give the brothers four more days.

Lincoln tells Michael that they have four more days to rescue Whistler, but Michael is upset with his brother that he used him. Gretchen has a meeting with General and they decide to use power to release Whistler in an operation called "Bang and Burn". Later she asks Whistler to kill Michael. In Sona, the guards reinforce the bars in the windows, and Michael tells Lechero that this way it will be difficult to break-out. Sammy requests more men to Lechero to keep Sona under control. Sofia receives a call from Whistler's mysterious landlord telling that he has some "insurance papers" from her boyfriend, however, the Company intercepts the conversation. When Sofia receives the documents, she finds a passport of Whistler in the name of Gary Miller. But Gretchen arrives and takes the documents. Mahone tells Agent Lang how he killed Shales and then high from the pills, asks her to get some drugs for him otherwise he will not be able to speak in the hearing. T-Bag gives a message from Lechero with the blueprint of his cell with a hidden door and an access code. Whistler is ready to stab Michael when Lechero arrives and he hides the knife. Michael asks McGrady to request his father to call Lincoln and give him a message: "Don't come home for dinner." Mahone fails in the hearing and is sent back to Sona. Lincoln, Sucre and Sofia are attacked by the Company's agents and the brothers realize that something is happening, i.e., the Company does not need them anymore. When the "Bang and Burn" Operation begins, Michael catches Whistler and Gretchen fails in her intent. General Zavala has Michael hauled in for questioning over the attempted breakout.

After the helicopter fails to break out Whistler, Sona's new commander, General Zavala, decides to make Michael talk by putting him into a sun-exposed isolation hot-box. He promises to help in exchange for the truth, verifies the L.J. situation and is told it's about Whistler. Whistler, realizing the tunnel is a no-go without engineer Scofield, denies knowledge blatantly to Zavala and is threatened with torture, until he admits to collaborating with Michael, who convinces him to give up Susan/Gretchen's name. Meanwhile Lincoln, is given a short meet up with L.J. as motivation. Mahone is back in Sona, desperate without his drug. T-Bag and his allies are mainly concerned with Lechero's expected succession and another bare-knuckle fight, won by Bellick. Gretchen recruits Sucre as a double spy (or triple for Linc); then General Zavala arrests and tortures her. Only Whistler's admission makes her admit L.J.'s kidnapping and leads them there, but she manages to kill the General and escape. Michael and Whistler are returned to general population, Mahone and T-Bag join the tunnel escape party. Lechero's cousin Augusto, now calls on Sammy to open the package - a gun.

Sammy reminds Lechero that Papo is dead and presses Lechero to kill Michael. Lechero replies that he also wants Michael dead, but he does not want an uprising in Sona. Mahone receives a picture of his son through the mail. Lechero, Michael, Mahone, Whistler and T-Bag inspect the hole in the tunnel and Michael requests a saw and hammer to support the tunnel. Sammy takes the over the reign of Sona with the pistol delivered by Augusto and other three gangsters and promises a box of bottles of rum for the inmate that kills Michael. T-Bag convinces Bellick to give the chicken foot to Sammy, promising him a spot on the escape team. When Bellick discovers that there is no more acetone, he unsuccessfully tries to call-off the fight. Meanwhile Lincoln and Sofia visits Osberto and buy a bomb. Sucre plants the bomb under the seat of Gretchen's car but she unravels that, saying she found Maricruz tracking the US$ 25,000.00 check she gave to him. Sammy leaves the fighting with Bellick to chase Michael, who is locked behind the door in the tunnel with Mahone. Sammy beats Whistler, who was left behind, trying to get the combination of the door. Michael removes a wedge from the hole and the tunnel collapses over Sammy, burying him, while Lechero and Mahone kill the three other gangsters. Sofia finds a wallet hidden in Whistler's bag.

As Michael finalizes plans for the escape, his fellow plotters begin to turn on him. Meanwhile, Whistler ponders a betrayal when Sofia is threatened.

Michael, Whistler, Mahone and McGrady escape from Sona - but not everything goes according to plan, and the exchange is compromised.

LJ and Whistler are exchanged, but more surprises abound. Meanwhile, T-Bag's scheming finally pays off.

Michael, Mahone, Sucre and Lincoln try to get into the house where Scylla is being kept safe. T-Bag and Sancho head to San Diego in the desert.

After the general catches the brothers and raises the stakes by abducting more of their relatives, Michael escapes with Scylla.