- The Prologue
In the prologue, Thomas goes through the Swipe and is put in the Box, as he is one of the candidates needed inside. He is told that Teresa will get the Swipe as well. Thomas is then sent into the Maze with Teresa, setting the events of The Maze Runner in motion.
- The Main Story
Set thirteen years before the prologue and events of The Maze Runner, the novel begins in New York City when the world is hit by catastrophic solar flares.
Mark and Trina form an alliance with Alec, Lana, and others who rescue them from a group of street urchins. The group flees to the fictional Lincoln building to avoid an impending tsunami. They camp out in the building for weeks until a yacht arrives and the ship's crew takes them hostage and kills one of them. Alec manages to overcome their captors and they take the yacht as their own, and they pilot the boat to the Appalachian Beaches.
The story resumes one year after the tsunami in Asheville – a small North Carolina village where Mark, Trina, Alec, and Lana now live. Huge helicopter-like vehicles called Bergs arrive and attack the people in the village; the Berg crew showers Asheville with darts that kill many villagers. Alec and Marc manage to subdue and take over a Berg but its pilot crashes the vehicle to avoid answering questions. They work out that the darts contained a deadly virus, and start their long journey back to Asheville.
Three days later they reach the village to find that the virus had killed most of the infected. Lana and Trina explain that after the initial death toll, people started living a little longer before dying; symptoms of infection also changed. Mark and Alec explain that the darts were filled with a virus and the group suspects that the virus is mutating.
Trina and Lana take Mark and Alec to a locked room where one of their other friends is confined. He had started having hallucinations, apparently due to the virus, and begged Trina and Lana to lock him up and they did so. Their sickening friend started saying that "They" were in his brain, eating it away. He kept repeating that "They" were going to eat at his head until nothing was left. He suddenly starts banging his head against a wall to silence "Them" and ends up killing himself.
Another girl who was his friend goes into the room and comes out reporting a headache which alarms Mark and Alec. They tell Lana and Trina to lock her up as well. Immediately after they confine, she starts acting just like her dead friend, talking about "Them", and starts to sing an eerie song about death.
Mark and Alec take Lana and Trina to find the mysterious attackers' base. The group passes through an abandoned village where they meet a 5-year-old girl named Deedee, whom they take with them. She tells them that just like Asheville, her village was attacked months earlier. The people turned crazy and left her behind. She shows the group a puncture mark that alarms Alec, who tells the group that Deedee must be infected. They decide to take her with them, anyway, since if she didn't have symptoms over months after being infected by the virus she was obviously immune to it.
While traveling to find the attackers' base, Mark and Alec leave the group for a while to investigate a loud noise. They encounter a cult of infected people, who believe that since Deedee is not affected by the virus like they are, she must be some sort of demon. Mark and Alec manage to escape from the cult but find that a forest fire has been started and that Trina, Lana, and Deedee are gone from their campsite. Believing that the three girls in their party must have escaped and gone ahead of them to the attackers base, Mark and Alec continue on to the site.
They arrive at the base and sneak into what appears to be the Post-Flares Coalition's (PFC) site. They eavesdrop on a conversation and realize that the disease is widely known as "the Flare", caused by a virus that shuts down the thinking-part of people's brains. They also learn that the girls were given back to the infected cult. They are caught eavesdropping but manage to escape and steal a Berg. Mark and Alec find a weapons inside the Berg called transvices – guns that evaporate people's molecules. They recharge one to use to battle the infected. Mark realizes that the Flare has started to affect his mind.
Their journey inside the Berg takes them near Asheville, where they find Lana suffering badly from torture by the infected; to end her suffering Alec must kill her with the transvice. They find Trina and Deedee at an old house, but Mark realizes that Trina also has the Flare and has forgotten him. They are attacked by the infected, but manage to escape to the Berg. As Mark starts to lose his sanity, he recognizes that Deedee is truly immune to the virus and should be sent to the safety of the PFC base in Alaska. Mark plans on delivering Deedee using a teleporter called a flat trans inside a PFC base in the safe part of Asheville. As they travel, they find that Alec is also dying from the Flare.
Mark and Trina manage to bring Deedee to the flat trans and send her through it to safety at the Alaskan PFC base. Mark orders Alec to crash the Berg into the flat trans building to prevent the infected from escaping Asheville. Trina remembers Mark and they kiss just as the Berg crashes, killing everyone in the base.
- The Epilogue
In the book's epilogue, two years later, authorities from WICKED take a little boy named Stephen away from his mother, because he is immune to the virus. They rename him Thomas.