Thomas is sleeping in the dormitory with the other teenagers, known as the Gladers, who escaped from the Maze in the previous book and had been brought by a group of rescuers. Thomas is woken by a telepathic communication with Teresa, the only girl from the Glade, who is afraid.
As Thomas wakes up, he finds that the facility is being attacked by Cranks, aggressive zombie-like people that have been infected by a plague known as the Flare. The disease attacks the brain and causes victims to lose their humanity, rendering them violent and insane creatures. Cranks were normal citizens before the Flare, when they became crazed zombie-like killers.
Thomas and the others escape into the facility's common area and discover that their rescuers are dead. They also find that Teresa is missing from her room, and in her place is a boy, Aris Jones. Aris explains he escaped from a similar Maze experiment, Group B, in which he was the only male. The boys then discover tattoos on their necks that assign them specific roles and fates. Thomas is stunned by his tattoo as his fate was written as “to be killed by Group B” which makes him worry more.
The Gladers re-enter the common area and find that the bodies of their rescuers have disappeared. Since nothing has changed, the Gladers almost die of starvation. Thomas takes a rest and after waking up, he finds Minho with an apple. They meet a scientist from WICKED, described by the boys as 'Rat Man' because of his rat-like appearance, who explains WICKED has been studying them to try to find a cure for the Flare. He tells them they have been infected with the Flare and in two weeks must get through the Scorch, the most burned-out section of the Earth after the sun flares, to find a safe haven and get the cure. To get into the Scorch, the Gladers go through a Flat Trans, which is a type of portal that closes five minutes after the set hour.
The Gladers travel to the Scorch through the Flat Trans and find themselves in a tunnel filled with metal slicing mechanisms that kills at least two Gladers and nearly kills Winston. They escape into the desert and find a building in which a girl is screaming. Thomas discovers that the screaming is artificial and enters the building to find Teresa, who kisses him and tells him that he needs to stay away from her.
As the Gladers search for supplies, Thomas begins to recover memories of the relationship that he had with Teresa before his memories were removed. They travel to a distant city, but are caught in a lightning storm that wipes out half of the group and kills Winston and Jack. They take refuge in a building and find a group of Cranks led by a man named Jorge. Minho attacks Jorge, so Jorge sentences him to death before Thomas talks him out of it. Thomas also convinces Jorge and his second-in-command, the teenage girl Brenda, to help the Gladers escape in exchange for some of the cure. Thomas and Brenda get separated from the rest of the group, and Thomas discovers a message written all over the city that says that he is the real leader. After a quick meal, the group is attacked and separated. Thomas and Brenda are then suddenly captured by another group of Cranks, who get them high on drugs and hallucinating. Brenda tries to kiss Thomas before they pass out, but he refuses her advances because of his feelings for Teresa and insults her, saying that she could never be Teresa.
Minho rescues them with the help of the other Gladers, but Thomas is shot in the shoulder with a rusty bullet that leads to an infection. Thomas's wounds get worse, and WICKED takes him aboard a flying vehicle, called a Berg, to heal his infection. A healed Thomas is returned to the Gladers, where Thomas explains that WICKED never wanted him to get shot and considers him very important to its plans. Thomas later receives a telepathic message from Teresa that warns him something terrible is about to happen, and she cannot help him.
The Gladers come across Group B, now led by Teresa. Group B takes Thomas prisoner, and Teresa says that she plans to kill him. Some of the other Group B girls tell Thomas that Teresa had never liked him and that their earlier kiss had been against her will. The girls, Harriett and Sonya, tell Thomas that they are not going to kill him and that Teresa is unhappy about the situation.
Later, Teresa comes to Thomas with Aris. Teresa and Aris kiss passionately and tell him that they've known each other longer than Thomas may have thought, and she explains that she has been manipulating Thomas all along. They lock Thomas in a room, where he passes out. While unconscious, he remembers some of his past relationship with Teresa and Aris before he entered the Maze. Eventually, Thomas is rescued by Aris and Teresa, who explain that they were forced by WICKED to make Thomas feel totally betrayed and that if they had not complied, WICKED would have killed him. Thomas is conflicted and no longer trusts them.
The Gladers and Group B reach the place that the safe haven is supposed to be as another lightning storm approaches. However, they are attacked by monsters created by WICKED until another Berg arrives from WICKED. They fight their way on board. WICKED, however, will allow either Jorge or Brenda to board, and the one not chosen to stay will be killed. Thomas chooses Brenda in the hope that WICKED will take whoever he does not choose. When it fails to do so, he overpowers the guard and forces him at gunpoint to allow both of them to remain on the Berg. The guard agrees and tells them that it was yet another test.
Later, as they rest, Teresa communicates telepathically with Thomas, who awakens separated from his friends in a plain white room and after he was left in isolation for a long time. Teresa tells him telepathically that the others are being told he has succumbed to the Flare. Still not trusting her, Thomas tells Teresa to leave him alone. She tells him "WICKED is good" before she cuts off communication.
The epilogue is in the form of an email from Chancellor Ava Paige, who writes that WICKED will soon tell the Gladers whether or not they are immune to the Flare.
