Thomas arrives in a place known as the Glade, left with no memories except his name. He meets other teenage boys called Gladers who have created a community. Each Glader is assigned to a task in different departments headed by a Keeper. Shortly after arrival, Thomas gets a tour by Alby, the oldest and the leader, and some other Gladers.

A gigantic maze surrounds the Glade. Inside, mechanical creatures called Grievers roam it at night. The huge doors into the maze close at sunset and reopen in the morning. Every week supplies are sent, and every month a new boy arrives in an elevator called, "the Box," It is the same elevator Thomas arrived in. There are also Beetle Blades, mechanical bugs which spy on the Gladers, with "WICKED" (World in Castastrophe - Killzone Experiment Department) written on them.

After Thomas arrives, an unconscious girl arrives carrying a note reading, "She's the last one." She is taken to the infirmary to recover from a coma before being questioned. Meanwhile, Thomas learns that the Gladers have unsuccessfully been trying to solve the Maze for two years, and that the antidote to a Griever sting revives small bits of memory. Chuck (a twelve year old boy), and Newt (the Gladers' second-in-command), befriend Thomas. Gladers exploring the Maze are called "Runners." Minho, the Keeper of the Runners, and Alby, the Gladers' leader, search for a dead Griever that Minho found while running the maze the day before. However, the Griever is found to be not dead and it stings Alby. Minho struggles to carry Alby back to the Glade, but as the doors close on them, Thomas runs into the Maze to help.

Hearing approaching Grievers, Minho leaves Thomas with an unconscious Alby. Thomas saves Alby and, finding Minho, tricks pursuing Grievers into falling off "the cliff" (an abyss within the Maze). Minho and Thomas return to the Glade as the doors open the next morning.

As the acting leader, Newt calls a "Gathering" to decide Thomas's fate for entering the Maze without permission. It is decided to make Thomas a Runner after serving one day in "the Slammer" (jail).

The day after, Thomas joins Minho running the Maze. They quickly discover a "Griever Hole" through a cliff, exposing the outside world. He also discovers words covered in vines that say, "World in Catastrophe: Killzone Experiment Department", assuming that WICKED is the acronym.

After returning to the Glade, Thomas is shocked that the girl speaks telepathically to him. Her name is Teresa, and she says she has triggered an "Ending." Soon afterward, Teresa awakes and befriends Thomas. The same day, the sky turns a dull gray, which Thomas attributes to the Creators of the Glade. That night, the Maze doors remain open, leaving the Gladers unprotected from the Grievers. The Grievers start taking one person each night. Alby also burns down the map room, but Minho and the other Runners had moved all the maps to a secret room. The Gladers align the maps, which spell out words. They have no relation to each other, and the Gladers determine it is a code.

Desperate to retrieve his lost memories, Thomas allows a Griever to sting him. After recovering, Thomas explains that he and Teresa were forced to help the Creators design the Maze. He says he and Teresa share a telepathic link. The way out of the Maze is over a cliff face and that it is an illusion to trick them. This is where the Grievers enter and exit the Maze. By following the Grievers, they can escape by punching the code words into a computer on the other side. Thomas leads the Gladers into the Maze and they confront a small army of Grievers. About half the Gladers die, but Thomas, Teresa, and Chuck escape down the hole and punch in the code and shut down the Maze. A door opens nearby.

The 21 remaining Gladers descend down a spiraling slide that dumps them into a massive underground bunker. There they meet the Creators: thin, pale, joyless adults who take copious notes while observing them from behind glass. A woman greets the Gladers, telling them they have done well. Gally appears pulls a gun on Thomas and fires. Chuck dives in front of it, sacrificing his life to save him. Enraged, Thomas kills Gally with a spear.

Suddenly, a group of gunmen storm the room and shoot the woman and the Creators. The Gladers are taken out of this facility and put into a large bus. As they are boarding, a hideously scarred woman grabs Thomas and tells him that he is here to save everyone from the Flare before the driver runs her over. Thomas and Teresa learn from a rescuer that the world was ravaged after solar flares slammed Earth, killing millions within days, leaving the world a wasteland. A disease known as the Flare now threatens humanity. The group's goal is to stop the tests WICKED is doing, and find the cure for the Flare.

After two hours, the bus stops at a dormitory-like building. Inside, the Gladers find bunk beds with blankets, bathrooms, and food. They finally feel safe. Thomas drifts off to sleep feeling there is hope for the future.

In an epilogue, it is suggested that the apparent rescue of the Gladers is yet another test masterminded by the Creators of the Maze and that the one Thomas escaped is not the only one WICKED have been observing.