- Thomas (Named after Thomas Edison): The main protagonist of the series. He is a teenage boy who was a Runner of Group A (the Gladers) before escaping the Maze with his fellow Gladers in The Maze Runner. He continued this by crossing the Scorch in The Scorch Trials, in which he was continuously manipulated by almost everyone, making it hard for him to trust other people again. Thomas escapes from having his memories restored in WICKED's headquarters and becomes entangled in the conflict between WICKED and the Right Arm – a rebel organization that opposes it. During the events in The Death Cure he loses several friends, including Newt, one of his best friends.
- Teresa (Named after Mother Teresa): A friend of Thomas. The only female Glader of Group A. In The Scorch Trials she betrays Thomas on WICKED's orders, causing him to distrust her. She volunteers for her memories to be restored and moves with the other Gladers to Denver. She eventually turns against WICKED. She dies after saving Thomas from being crushed by falling debris.
- Newt (Named after Isaac Newton): Newt goes through the most out of all the other characters. He took upon the role of the leader of Group A after their previous leader, Alby, died in The Maze Runner. He is Thomas' closest companion, alongside Minho. The book reveals that Newt is not immune to the Flare virus and is slowly succumbing to its influence. Eventually, he begs his best friend, Thomas, to save him from the virus inside him via euthanasia, which Thomas does.
- Minho: A Glader, and the former Keeper of the Runners of Group A. He was Thomas' fellow Runner back in the Glade and throughout the series becomes one of Thomas' best friends throughout their Trials, joining him to escape WICKED's attempt to restore their memories and save the Immunes from the Maze.
- Brenda: A Canadian girl, was part of a group of rebels in The Scorch Trials before being separated and having to navigate her way through the Scorch. She shares a mutual attraction with Thomas.
- Jorge: The leader of a group of rebels the Gladers met in The Scorch Trials. He has a close relationship with Brenda. Brenda described their relationship as Jorge being "like an uncle" to her. He was revealed to be working for WICKED but helps Thomas, Minho, and Newt escape from WICKED's headquarters and remove their chips.
- Aris (Named after Aristotle): The only male member of Group B. He met Thomas in The Scorch Trials. Aris, Thomas, and Teresa are close friends in The Scorch Trials.
- Janson (Rat Man): The Assistant Director of WICKED and the book's main antagonist. He is succumbing to the Flare virus, which explains his desperation for a cure. He arranges for the Group A and Group B survivors' memories to be restored, but wants to make them go through the Trials again. Eventually, Thomas kills him by strangling him, after Janson and other WICKED members try to recapture the surviving Immunes.
- Gally (Named after Galileo): A Glader of Group A who strictly followed the rules of the Glade and thus became Thomas' adversary in The Maze Runner. He indirectly caused Chuck's death when Chuck intercepted a knife Gally had thrown at Thomas. In this book, he reunites with Thomas and reveals he has been working with the Right Arm, an organization determined to stop WICKED. However, after discovering the Right Arm's true purpose, he left with Thomas and the Gladers to rescue the Immunes in the Maze.
- Vince: The leader of the Right Arm, an organization opposed to WICKED. He is Gally's boss. He recruits Thomas to infiltrate the WICKED headquarters and plant a device inside that disables the WICKED's weapons, and then leads the Right Arm's invasion of WICKED. He is strictly dedicated to his cause and brands Thomas and Gally traitors when they attempt to save hundreds of Immunes hidden in the Maze, which is about to be destroyed by the Right Arm.
- Lawrence: Vince's assistant, who captures Thomas, Minho, Brenda, and Jorge and delivers them to a safe house. After their demands to see "the boss" Lawrence took them to Vince. He later drops off Thomas near the WICKED headquarters for his plan to plant the explosive device.
- Hans: A former WICKED scientist whom Thomas, Minho, Brenda, and Jorge, meet in Denver to help remove the chips from Thomas and Minho.
- Ava Paige: The Chancellor of WICKED and the person responsible for managing and organizing the search for a cure of the Flare, including sending teenagers into the Maze to study the minds of Immunes. However, she disagreed with the consequence that the teenagers were being killed. Her character serves as the omniscient voice in the books' Epilogues. She was never seen in the series, but every Epilogue of the three books in the main series, plus The Fever Code, includes an email she writes to her associates. She states a cure for the Flare virus will never be found, that the Immunes are humanity's last hope to restore the dying world, and that WICKED's actions of sending them for Trials are threatening that hope. She serves as an ex-machina in the narrative, saving Thomas from a fatal brain experiment at the last minute after he was sedated; She instigates and secretly orchestrates his rescue of hundreds of Immunes from the attack on the Maze. She also promises and delivers a paradisaical safe haven for the Immunes.
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