First Down is the 26th episode in the series and the 4th in season 2. In this episode, Bellick shacks up with Michael, Lincoln and Nika in hopes of discovering Westmorelands hidden $5 million; a family learns the dangers of hitchhiking when they pick up a stranded T-Bag; Abruzzi rejoins the family and is determined to get his revenge on Fibonnoci; Kellerman makes his move on Sarah, who gets a phone call she has been waiting for; and Mahone finally gets his man.
Lincoln spots a tail as he drives down a rural highway. Michael and Nika turn around to see Bellick and Geary following them. Geary speeds up next to their car and attempts to ram their car off the road. He succeeds in forcing their car down a ditch, hitting a tree. Bellick points his pistol at Lincoln, Michael and Nika as he tells Michael that he knows about the money in Utah and has decided to join them on their trip to pick up the money. Bellick forces them to get into his and Geary's car.
At the field office of the FBI in Chicago, one of Agent Mahone's subordinates inform him that 12 percent of the data from Michael's hard drive, which he dumped in the river, has been recovered. These included the newspaper clippings of Abruzzi, Sara and D. B. Cooper's money. Another agent then tells him about the positive match on the blood results - B negative, the same as Michael and Lincoln's blood type. Mahone becomes agitated and tells all the agents in the office to not to announce deaths until they are confirmed, and orders them to do more tests.
Bellick and Geary are forced to stop when one of their car tires go flat, which Lincoln had secretly stuck a shard of glass under. Bellick proceeds to tell Geary to go to the nearest town to buy a tire and force Michael, Lincoln and Nika into the neighbouring woods. Tied up in an isolated building, Lincoln tells Michael that he doesn't trust Nika. In the meantime, Nika negotiates with Bellick, convincing him that she wants Michael dead, that Michael was trying to set up Bellick in Panguitch, Utah, and that she will sleep with Bellick for a share of the money in Utah. Whilst seducing him, Nika tries to steal Bellick's gun. Bellick returns her to the other room and tells her not to try and fool him. As he walks away, he realizes his knife was stolen, as Lincoln frees himself and uses the knife against Bellick. Upon Geary's return, both Geary and Bellick are tied up. Bellick tells Michael about Sara's overdose.
Kellerman, posing as Lance, tells the other recovering addicts at a Narcotics Anonymous meeting an emotional story, about his mother dying of multiple sclerosis and hinting that he may inherit it, knowing it is not genetic and will attract attention from Sara. After the meeting, Kellerman approaches Sara and begins to talk with her, trying to befriend her. As they eat their pies, Sara receives a call from Michael. Michael begins to apologise for everything that has happened to Sara, who does not want to talk to him. He insistently tells her that there is a way he can protect her and "it" is already in her possession. Sara is confused about what he is talking about. Kellerman looks up after hearing Sara calling for Michael, who had hung up.
Tweener travels with Debra Jean in her Toyota Yaris, which was also extensively featured in the Prison Break mobisodes. When the radio talks about the Fox River Eight's escape, Tweener switches the radio to sing along - awkwardly to a John Denver song, Take Me Home, Country Roads. After Tweener spots a police officer, he tells Debra Jean to slow down even though she was only travelling at 65 miles per hour. Debra Jean becomes more suspicious of Tweener. Once the couple end up staying at The Lotus Motel in Mack, Colorado, Debra Jean relays her location on the phone to somebody.
T-Bag stops at a gas station in Friend, Nebraska. The police surround the SUV T-Bag stole from the murdered Dr. Gudat while he is in the station restroom. T-Bag pretends to be a former US Marine wounded in Kandahar, Afghanistan. He blames the stolen SUV on the "hippie" in the gas station restroom. The hippie was quickly taken into custody. Forced to abandon the SUV, he becomes a hitchhiker and is picked up by an unsuspecting man and his teenage daughter. T-Bag makes his perverted move, and the unsuspecting man attempts to attack T-Bag. T-Bag is able to knock out the man and steals his station wagon and hat.
In Brooklyn, New York, John Abruzzi reunites with his family. One of his mafia associates tells him that Otto Fibonacci is going to testify in Washington, D.C.. Abruzzi decides to get his revenge instead of hiding on a cargo ship back to Sardinia, Italy. When Abruzzi is informed of Fibonacci's location, he's told that the information is "from New Jersey; Fish-Head Tommy wants to pay tribute." The lead on Fibonacci turns out to be fake, a setup not unlike Fibonacci's set up upon him. Abruzzi decides to go down fighting, and is swiftly shot by Agent Mahone's men.
Michael, Lincoln and Nika prepare to leave. Michael tells Nika he can take her into town. However, Nika wants to go with them. At Michael's refusal, Nika relents and hugs him, bidding him farewell. As she hugs Lincoln, she reaches round to take the gun from Lincoln and points the gun at them. Nika confesses her love for Michael. She proceeds to use the cell phone to call the police but is stopped by Lincoln, who had pulled out the gun's magazine clip earlier. He takes the gun and cell phone from Nika and gets in the car. Michael sadly wishes Nika luck and joins his brother in the car. They drive off leaving Nika standing alone on the side of the road.
Mahone receives the results of the lab tests which proves that the blood from the crash site was that of a pig. Reminded of his previous failure to capture Oscar Shales, Mahone unleashes his fury on the picture of Michael and says ominously to it, "You have no idea what you're in for."
- First Down refers to the first Fox River 8 casualty of the season (John Abruzzi).
- When Nika tells Burrows and Scofield how much legal money she could get by turning them in, she says $200,000. This is incorrect: the bounty on Lincoln alone is $300,000, plus the $100,000 on Michael makes $400,000.
- The newspaper clipping of Sara Tancredi that Mahone recovers from Michael's hard drive, which also appeared in Michael's apartment in the series premiere, states that her full name is Sara Wayne Tancredi. The actress who plays Sara is named Sarah Wayne Callies.
- This marks the last appearance of Peter Stormare as John Abruzzi. Abruzzi later appears in pictures and archive footage in season 2 and appears on a photo in Michael's dream in season 4.
- Amaury Nolasco (Fernando Sucre) and Rockmond Dunbar (C-Note) don't appear in this episode. However, they appear in pictures and may have been credited for their picture appearances.