Police informant Michael awakens in a room with a spike-filled mask locked around his neck. He refuses to retrieve the key from his eye and is killed when the mask closes on his head. At the scene of Michael's murder, Detective Kerry finds a message for her former partner, Detective Eric Matthews. Matthews joins Kerry and Officer Rigg in leading a SWAT team to the factory which produced the lock from Michael's trap. There, they apprehend John Kramer, the Jigsaw Killer, who indicates computer monitors showing eight people trapped in a house, including his only known survivor Amanda, Matthews's son Daniel, and six other victims: Xavier, Jonas, Laura, Addison, Obi, and Gus. A nerve agent filling the house will kill them all within two hours, but John assures Matthews that if he follows the rules of his own game, he will see Daniel again. At Kerry's urging, Matthews agrees to buy time for the tech team to arrive and trace the video signal. During their conversation, John reveals to Matthews that his main motivation for his games was a suicide attempt after his cancer diagnosis, which led to a newfound appreciation for life; the games are intended to help his victims develop the same appreciation.

The group is informed by a microcassette recorder that antidotes are hidden throughout the house; one is in the room's safe, and the tape provides a cryptic clue. Gus ignores a warning note and uses the key provided with the cassette on the door, which triggers a revolver through the peephole that kills him. Once the door opens, they search the house and find a basement, where Obi, who helped with abducting the other victims, is killed in a furnace trap while trying to retrieve two antidotes. In another room, Xavier's test involves digging through a pit filled with syringes to retrieve a key to a steel door in two minutes, but he instead throws Amanda into the pit. She retrieves the key, but Xavier fails to unlock the door in time. Throughout the game, the group discuss connections between them and determine that each has been incarcerated before except Daniel. During his father's test, John reveals their affiliation to Matthews, who was a corrupt police officer who framed his suspects in various crimes.