The film starts with hundreds of people crowded around a quarantined area. A young Thomas is brought by his mother to be taken away for protection onboard a train. She tells him she loves him and they never see each other again. On the train, Thomas meets Dr. Ava Paige (Patricia Clarkson).
In the present, Thomas (Dylan O'Brien) and the rest of the Gladers - Newt (Thomas Brodie-Sangster), Teresa (Kaya Scodelario), Minho (Ki Hong Lee), Frypan (Dexter Darden), and Winston (Alexander Flores) - are brought to the desolated city following their escape. Once they descend, a horde of infected people ("Cranks") start running towards them, but the mercs escorting them fight them off. They take the Gladers into a facility run by Janson (Aidan Gillen). He says this place will provide the Gladers with shelter, food, clothes, and protection from The Flare.
Thomas joins Minho and the other boys in a cafeteria. They see other groups of people their age, meaning they weren't the only ones that survived a Maze. Frypan points out one boy, Aris (Jacob Lofland), who has been in a Maze the longest, and in one with mostly girls. Janson then walks in and calls on the names of several people for what is supposedly a relocation. Teresa's name is called and she joins the others as they walk out.
At night, Aris gets Thomas out of bed and guides him through the vents to show him the room where a number of bodies are wheeled into a room for tests and research. Thomas starts to think they're doing something bad with Teresa.
The next day, another group of people are called out. Thomas gets into a brief scuffle with a guard to steal his ID badge. That night, he and his friends sneak out of their rooms to find Teresa and the others. Thomas encounters them all hung up to a mechanism of sorts, and all of them are unconscious. Thomas then walks into a room where he sees Janson talking to Ava through a projection. He's been running tests to see who is immune to The Flare, and he mentions trying to find a group called The Right Arm and their grounds called Safe Haven. Thomas realizes Janson works for WCKD.
Thomas gathers Newt, Minho, Frypan, Winston, and Aris, and tries to find Teresa so they can escape. They come across a merc who aims his stun gun at them, until Minho dropkicks him into a wall. Thomas grabs the gun and gets a doctor to take them to Teresa. They grab her and head out to the exit. Janson and some other mercs try to stop them, saying they won't last out their in The Scorch. Thomas fends them off and barely makes it out with the others.
Now on the outside, the Gladers venture toward the mountains to find The Right Arm. They come across an abandoned building and discover the place has power, but when they turn it on, Thomas and Minho find themselves attacked by some Cranks. They chase after the boys, then the rest of the gang once they run back into each other. As they find an exit, Winston holds them off with a gun, but one of the Cranks attacks him and scratches him. The others pull him out.
The Gladers continue walking through the mounds of sand as day breaks. Winston collapses, as he's been infected and it's spreading rapidly through his body. He only wants to be put out of his misery and not transform into a Crank. Frypan takes out a gun, which Newt takes from him and hands to Winston. Winston says his goodbyes to his friends, and they leave him. On their walk, they all hear a single gunshot.
As the others rest for the night, Thomas spots a civilization in the distance. When the gang keeps moving, a massive lightning storm starts brewing. Powerful bolts strike down, hitting Minho but non-fatally. His friends grab him and they run into another building. There, they find dozens of chained Cranks. Out of the shadows comes Brenda (Rosa Salazar), who lives there with a group of survivors. She guides the Gladers to her leader/surrogate father figure Jorge (Giancarlo Esposito). He notices the tattoos on the backs of the Gladers' necks, realizing they came from a WCKD facility and that they are valuable. Jorge also learns they are looking for The Right Arm.
Soon, a band of WCKD mercs, led by Janson, storms the place. Thomas runs away with Brenda, separating himself from the other Gladers. Jorge plays a song that triggers a series of explosives when it finishes. The facility collapses and kills the mercs. Thomas and Brenda run toward an exit as they are pursued by Cranks. They run outside into a collapsed building. Brenda slips and nearly falls through a window. A Crank emerges and attacks her, but Thomas breaks the glass and causes the Crank to fall out while he pulls Brenda up.
The two head on to find the others and come across a club of sorts, run by another survivor, Marcus (Alan Tudyk). He knows something about The Right Arm, but he doesn't tell Thomas and Brenda of his identity, and instead gives them a drink for them to get in the feel of the party. Thomas trips out a bit, and Brenda approaches him. They move in to kiss, but Thomas only sees himself kissing Teresa. He tells Brenda she isn't Teresa, leaving her disappointed.
After experiencing trippy visions, Thomas wakes up to find Teresa and Minho sitting over him. He and Brenda are back with Jorge and the Gladers, and Thomas finds Jorge beating Marcus's face in. After a few good punches, Marcus tells the gang where they can find The Right Arm.
The group takes Marcus's car and drives by a mountain with many abandoned cars. When they get out, gunshots are fired at them. Jorge hands Thomas a bomb to use a distraction, but they are cornered by two shooters, Harriet (Nathalie Emmanuel) and Sonya (Katherine McNamara). They recognize Aris and decide the group poses no threat to them.
The ladies guide the group to meet the rest of The Right Arm, including their leader Vince (Barry Pepper). Brenda collapses, as she's been bitten by a Crank, but her infection hasn't spread as quickly as with Winston. Vince nearly shoots her until he is stopped by a former WCKD scientist named Mary Cooper (Lili Taylor). She reveals that Thomas was an informant to share information on all of WCKD's acts. She gives Brenda an enzyme shot to stop the infection from spreading.
Thomas sits by Brenda's bedside. She mentions losing her mom to The Flare. Thomas pulls out the small totem given to him by Chuck, as he remembers the boy's sacrifice.
That night, Thomas talks with Teresa. She says that she watched her mom go mad from The Flare, and she didn't want to give up on the rest of the infected...which is why she's been working for WCKD the whole time. WCKD choppers are seen heading toward the mountains, as Teresa called them and told them where they are. Thomas runs to warn everyone, only for the choppers to start firing missiles at the people. The mercs descend and start attacking people. Thomas departs from Jorge and Brenda to save his friends. Ava and Janson step out, confirming that Teresa has been with the from the beginning. Janson shoots and kills Mary, and he nearly kills again until Jorge drives in on a van, leading to a battle between WCKD mercs and The Right Arm. Janson nearly kills Thomas until Brenda shoots him in the shoulder. Thomas uses Jorge's bomb on a group of mercs. Minho gets shot with a stun gun and is taken by the mercs. Ava, Teresa, and Janson escape with Minho as Thomas helplessly watches the craft take off.
In the morning, the survivors seem to have lost hope. Thomas gathers what he can carry and decides he's going to infiltrate WCKD, rescue Minho, and kill Ava. Although Vince thinks he's crazy, Harriet agrees that she wouldn't mind some revenge. Now, everyone looks to Thomas as they prepare to take WCKD down.
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