With hospitals and clinics under surveillance, Michael brings Lincoln to Nika's home to heal his wounded leg. Then he returns to the place where he parked his Accord and finds that the car has been towed. Meanwhile agent Mahone retrieves Michael's backpack with his passport from a vagrant that broke the rear window of Michael's car to steal the backpack. Michael goes to Brewster Towing yard to recover his car. Meanwhile Sucre finds that Maricruz will marry Hector in a couple of days and he heads to New York in a stolen car. Sara is arrested and her father visits her, pays her bail and orders her to tell a fake version about the incident in Fox River since he will be the next Vice-President of United States. Later she goes to rehabilitation where Kellerman is pretending to be an addicted patient. C-Note schedules a meeting with his wife, but his conversation is bugged by agent Mahone. Bellick and Geary meet each other by chance and later they team-up to get the $400,000 reward for capturing Michael and Lincoln. They go to Fox River and Bellick interrogates Manche Sanchez, who discloses the plan of the fugitives. Michael and Lincoln forge a car accident to escape from Mahone, but they do not see that Bellick and Geary are in their tail.

Michael, Linc, and Nika are captured by Bellick and Geary, who intend to retrieve Westmoreland's money in Utah. Tweener continues his drive with Debra Jean. Abruzzi is reunited with his wife and children and is set to flee the country with them, but decides to take care of Fibonacci first. T-Bag has a close call with the police at a Nebraska gas station, and then poses as a Marine who lost his hand in Iraq. Mahone waits for confirmation of the deaths of Michael and Linc in the car explosion, and meanwhile gets a lead on one of the other fugitives. Kellerman (posing as a recovering addict named Lance) befriends Sara.

Michael and Linc arrive in Tooele, but the map they need to locate the double-K ranch is missing. They run into T-Bag and Tweener, who have also come to Tooele for Westmoreland's money. Meanwhile, C-Note makes his way by train toward Tooele. Sucre reaches Las Vegas and attempts to halt the wedding of Maricruz and Hector. Sara invites Kellerman to her apartment, believing he is harmless. At the FBI office in Chicago, Mahone reviews files recovered from Michael's hard drive, and begins to piece things together.

Michael tries to retrieve an item from Blanding Botanical Garden in Utah, but Mahone's people got to it first. Mahone believes that someone on his team is leaking information to the press; meanwhile Michael does some research on Mahone at an Internet café, then makes a trip to Durango, Colorado, to see a woman there. Linc and L.J. are on the road in Arizona. C-Note is in Chicago, and Agent Lang tries to use his wife to capture him. Bellick and Geary phone C.O. Patterson, at Fox River, to get information on where they should look for T-Bag. Sara is at a motel in Elgin, Illinois, trying to crack Michael's code. T-Bag arrives in Tribune, Kansas, for (as he puts it) "romance". Kellerman is on the trail of Sara.

Captain Bellick tortures T-Bag for the money during which T-Bag swallows the key and Bellick uses dirty tricks to get the key out.Bellick and Mac leave T-Bag on the boundary of the police.Sarah and Michael Scofield meet,but they are constantly chased by Alexander Mahone.Michael gets close to Mahone's helplessness.Meanwhile Lincoln Burrows and LJ are rescued by Lincon's dad but they are still not shielded from the dirty political games. Sucre tries to contact Maricruz but that plan fails because of the state police doing rounds.

In Cutback, Montana, Kellerman lures the police and Michael and Lincoln abduct the cameraman Greg of Fox News and succeed in escaping from the siege. Michael and Lincoln decide to tape a message to be released in the Breaking News. Mahone is back in Chicago and analyzing the message; he interrogates Greg and he tells that he had overheard Michael tell that they should cover 460 miles in six hours. Mahone deduces that they intend to meet President Caroline in Denver. Wheeler discusses with Mahone and yells that the Internal Affairs department asked him to follow all moves of Mahone. Bellick is badly wounded in the infirmary of Fox River. Sucre befriends an old passenger in a bus to Ixtapa; however the driver asks him to leave the bus in a small town and Sucre robs the Volkswagen of the old man. In Algoma, Winsconsin, Haywire befriends a young couple and the girl has bruises on her arm; she tells that her abusive drunken father beat her.

Michael Scofield and Sara Tancredi fail to get the tape from the Corona de Oro cigar club in Chicago, where security was at the ready, and turn to former warden Henry Pope, a club member, but he wants to call the police. Michael draws his gun and hands it over to prove his veracity; Sarah convinces him to go in with her late father's humidor key and he finds a computer memory stick. In Mexico, Fernando Sucre has car trouble and gets a ride from an Ixtapa airport security employee who sees his wanted-poster just after they parted at the airport, so he must run with his bride. T-bag and his forced-along family find his own house vandalized and looted except for the family bible, which arouses in him youth memories of his perverted father, and assures Suzy he wants their love and is happy to be infertile, her bloodline should take the Bagwells's place. When she refuses, he locks them up, considers ax-murdering but just leaves them behind. FBI Special Agent Alexander Mahone has tracked down Benjamin Miles 'C-Note' Franklin and his daughter, but lets them escape in a bus rather than shoot the kid. C-Note brings her to a doctor, worried about the kidney disease PKD, but won't allow inserting a catheter, rather turns himself in to Mahone, who is with his own boy in Colorado, and makes a deal to get him Scofield. Pope is out of the club, but is greeted at the entrance by Secret Service Special Agent William 'Bill' Kim whom only Paul Kellerman, watching from a roof with Linc, knows by sight. Michael drives over Kim and gets away with Pope, Sarah and Linc, locking Kellerman out. When Michael tells the others he's prepared to honor his promise to Pope (which the others didn't know about) to turn himself in for his help, Henry hands him the stick and lets them go.

Captain Brad Bellick walks in the FBI office demanding Mahone pay him. Michael and his companions are impressed with the recordings on the stick, but it only helps if Kellerman's contacts in Washington use it right, notably high Justice official Cooper Green, who agrees to meet and cooperate, but is tailed by Kim's men. Linc calls his boy L.J., who refuses to give up his relatively normal life till further notice. Sarah meets Bruce Bennett. Bellick tries to bribe Sucre's incarcerated cousin into betraying his Mexican whereabouts. T-Bag finds therapist Dr. Stammel who looks like him, and murders him to steal his identity. Mahone is ordered to dispose of C-note for good once Kim believes he has Scofield; he promises to keep taking care of C-note's family, but only if he uses the content of a package he'll send to his cell- a noose. Sarah is too late calling Linc the real Cooper Green is in his office, but Michael tricks the fake one who pretended to be asthmatic just in time and knocks him down. Paul Kellerman visits his sister Kristine. Fernando Sucre is in heaven in bed with Maricruz Delgado when their baby kicks. The real Cooper Green could help with the tape, but then finds the memory stick has the copy date, not the recording date without which it is not admissible as proof, only to blackmail the president into signing a pardon.

C-note has jumped with the noose around his neck, but is saved by jailers; he has Mahone told he'll still do it. At a Chicago hotel, president Caroline Reynolds is expected for a speech. Michael sends the real Cooper Green away and agrees a meeting point with Linc and Sarah. Mahone enters Sarah's room and only pretends to fail looking under the bed to trap her, she pretends the brothers left her. In Mexico, T-bag finds Bellick is waiting at the luggage conveyor and must get his from the service side, but the laborer he knocks down falls onto it, so he must run. Lincoln surprises his old mate Derrick Sweeney and calls a favor: three tickets on a freighter for Panama. Kellerman is in position to shoot the fiendish president, but when she's in his sight Michael gets arrested just after shaking her hand, and is interrogated by Kim who demands to be left alone with him, to ask where Linc is, then tries literally to beat it out of him; the president barges in and sends Kim out just when he was about to shoot Michael; he tells her the tape is a delicate conversation she had with her brother after his 'death', and he still has copies at twenty locations. Fernando sees on TV T-bag is in Mexico and was videotaped trying to steal, so he deduces the $5,000,000 must be around and tells Maricruz he'll be right back; at his return only Bellick is there, armed and cuffs Sucre, in order to collect the reward, so Fernando offers to share the $5,000,000 by finding T-bag. Sarah guesses right Mahone is on an addictive drug. Caroline calls Linc, who plays the tape which proves her brother was alive on the isle of Terrence and hated conspiring with her Linc's faked conviction; Michael tells her about his suicide and dares her to make a decision: let him walk and sign a pardon for both brothers the very day, on live TV; Kim fails to stop him being released and walking out. When the phone rings, Sarah surprises Mahone and escapes- actually he arranged this and has her followed. Kim talks to a grim man in power; Reynolds announces on TV she has a malignant cancer and resigns immediately.

Now that Caroline Reynolds has stepped down as president, she can no longer sign a pardon, so the brothers must immediately disappear, forever. At the pier Sarah realizes she's being tailed and pretends on the phone already to be on board, so they sail without her while she is arrested. Lincoln stops Michael from returning for her. A week later, an FBI bigwig offers C-note a lesser sentence for testimony against Mahone, even freedom and witness protection for his family- bingo. Fernando grabs Bellick's gun while looking for T-bag, but Bellick shows a crucifix to prove he has Maricruz. The scumbag enjoys his fortune with a lady of the street playing his Susan-Q. The brothers arrive at Cristobal, Panama. Meanwhile Malone's team deduces Scofield's tattoos refer to Michael's mother Christina, presumably dead, and he presumes his computer contained much info on Panama for a reason. The man in power grills Kim on a small boat, and decides to change the strategy. Mahone sees through FBI-colleague Wheeler. C-note is reunited with his family and released. The brothers have a fight, torn by guilt for too many innocent people suffering through their well-meaning deeds, then board a yacht, named- Christina. Mahone tells Kim he's not happy with the results as he remains separated from his family, but is told he now needs help to escape, and therefore must go to Mexico- to help T-bag.

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.

Michael and the team have one day to locate the next cardholder or they risk going back to prison. Meanwhile, Mahone seeks revenge on Wyatt.

Don and Gretchen, Michael and The Company are all after Scylla. Elsewhere, T-Bag has to make a tough decision as he holds Gretchen's family hostage.

When Michael undergoes surgery, he has visions of Westmoreland. Meanwhile, Lincoln and Sucre try to retrieve Scylla before Don and Gretchen sell it.

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

Michael and Sara's newfound happiness is short-lived, as Sara soon finds herself in prison, and Michael must break her out before a vengeful Krantz has her killed.