Informant Michael Marks awakens in a room with a spike-filled mask locked to his neck, a video tape informs him that in order to unlock the device, he must cut into his eye to obtain the key, which has been sealed behind it. He sets off the timer and finds the scalpel, but cannot bring himself to retrieve the key and is killed after 60 seconds when the mask closes.
At the scene of Marks' game, Detective Allison Kerry finds a message for her former partner, Eric Matthews, and calls him in. Despite not wanting to be involved with the case, already dealing with a divorce and estrangement from his son Daniel, Eric reluctantly joins Kerry and Sergeant Rigg in leading a SWAT team to the factory which produced the lock from Marks' trap. There they find and apprehend John Kramer, the Jigsaw Killer, who is weak from cancer. He indicates several computer monitors showing eight people trapped in a house; among them are Amanda Young, the only known survivor, and Daniel. A nerve agent filling the house will kill them within two hours, but Kramer assures Eric that following his own game, simply sitting and chatting with Kramer, will see Daniel returned to him unharmed. At Kerry's urging, Eric agrees in order to buy time for the tech team to arrive and trace the video signal.
The victims are informed by microcassette recorder that antidotes are hidden throughout the house; one is in the room's safe, and a cryptic clue is provided. Xavier ignores a warning note and uses a key on the door, which fires a bullet through the peephole and Gus' eye, killing him. They search the house for more antidotes after the room lets them out, with no success: Obi, who is revealed by tape to have helped with the abductions, is forced into a furnace to obtain two antidotes inside, but inadvertently activates the trap and is burned to death before the others can save him; In the next room, Xavier throws Amanda into a syringe-filled pit intended for himself, and though she is able to retrieve the key, he is unable to unlock the steel door behind which the antidote sits before the timer expires and he leaves out of frustration. Throughout the game, they discuss connections between them and determine that each has been jailed before; the sole exception is Daniel, who has nonetheless been arrested before.
Meanwhile, Kramer passes the time with both idle and cryptic chat, eventually telling Eric that his survival of a suicide attempt after his diagnosis is the true reason for his games. With the little time left to him, he wants to inspire in others the new appreciation for life he had found. Eric, not interested in any of this, runs out of patience and returns to the monitors. He destroys several of Kramer's documents and sketches at Kerry's suggestion, but fails to provoke Kramer. As the tech team arrives, Kramer reveals the connection between the victims: Eric has framed all of them for various crimes, and Daniel will be in danger if his identity is discovered.
Having left the others, Xavier returns to the safe room and finds a colored number on Gus' neck. After realizing the answer to the clue, he kills Jonas with a spiked bat for his number after a brief fight and begins hunting the others. Laura succumbs to the nerve agent after finding the clue revealing Daniel's identity. Addison and Amanda abandon him, but Amanda returns after finding Jonas' body. Addison finds a glass box housing an antidote, but her arms become trapped in the bladed arm holes, and Xavier leaves her to die after reading her number. Amanda and Daniel find a tunnel in the safe room which leads to a dilapidated bathroom with two rotting corpses. Daniel collapses inside just before Xavier finds them. Amanda notes that he can't read his own number, and he cuts the skin from his neck. As he approaches, Daniel, who feigned his collapse, jumps up and slashes his neck with a hacksaw, killing him.
Having seen Xavier chasing his son, Eric brutally assaults Kramer and forces him to lead Eric to the house. Kramer's sitting area is revealed to be a lift, which they use to leave the factory. The tech team tracks the video's source and Rigg leads his team to a house, where they find VCRs playing previously recorded images. As Kerry realizes the game took place before they found Kramer, the timer expires and a large safe opens, revealing Daniel bound and breathing into an oxygen mask. Eric enters the house alone and eventually locates the bathroom, where he is attacked by a pig-masked figure. He awakens shackled at the ankle to a pipe; a tape recorder left by Amanda reveals that she intends to continue Kramer's work after he dies. Amanda appears in the doorway and seals the door, leaving Eric to die. Outside, Kramer hears Eric's screams and slowly smiles.
Who assaults Kramer?
Eric