Wiping out the human race? That's a great idea. That's great. But more of a long-term

              thing.  I mean, first we have to focus on more immediate goals.

James Cole (Willis) is a convicted criminal living in a grim post-apocalyptic future. The Earth's surface has been contaminated by a virus so deadly that it killed five billion people in 1996 and 1997, forcing the surviving population to live underground. Cole is forced to "volunteer" on a mission to the surface in a barren Philadelphia. He collects bugs and is returned to the underground where another mission is proposed. To earn a pardon, Cole allows scientists to send him on dangerous missions to the past to collect information on the virus. If possible, he is to obtain a pure sample of the original virus so a cure can be made, enabling the human race to return to the surface. Throughout the film, Cole is troubled with recurring dreams involving a chase and a shooting in an airport.

The scientists' time machine is imprecise. On Cole's first trip, he arrives in Baltimore in 1990, not 1996 as planned. He is arrested and hospitalized in a mental institution on the diagnosis of Dr. Kathryn Railly (Stowe). There, he encounters Jeffrey Goines (Pitt), a psychotic fellow mental patient. Cole tries unsuccessfully to leave a voicemail on a number monitored by the scientists in the future. After a failed escape attempt, Cole is placed in restraints and locked in a cell, but is then returned to the future, a disappearance which baffles his doctors.

Back in his own time, Cole is interviewed by the scientists, who play a distorted voice mail message which gives the location of the Army of the Twelve Monkeys and states that they are responsible for the virus. He is also shown photos of numerous people, including Goines. The scientists send him back to the past, and this time – after a brief detour to France (WW1), where he is shot in the leg – he reaches 1996.

Cole kidnaps Railly and sets out in search of Goines, who they learn is founder of the Army of the Twelve Monkeys. When Cole learns that Goines's father is a famous virologist, he becomes more than ever convinced that he's on the right track. When confronted, however, Goines denies any involvement with the virus and suggests that wiping out humanity was Cole's idea, originally broached at the asylum in 1990. Cole vanishes again as police approach.

After Cole disappears, Railly begins to doubt her diagnosis of Cole when she finds evidence that he is telling the truth. Cole, on the other hand, convinces himself that his future experiences are hallucinations, and longs to return to the pre-plague world and be with Railly. He persuades the scientists to send him back again. In 1996 Philadelphia, shortly before the initial outbreak of the virus, Railly attempts to settle the question of Cole's sanity by leaving a voice mail on the number provided by Cole. When she recites her message later, Cole remembers it as the message the scientists played prior to his second mission. They both now realize that the coming plague is real, and make plans to fly to Key West to avoid the virus.

On their way to the airport, they learn that the Army of the Twelve Monkeys is a red herring; all the Army has done is delay traffic by releasing all the animals in the zoo. Cole decides he has done his duty to the future. At the airport, he leaves a last message telling the scientists they are on the wrong track following the Army of the Twelve Monkeys, and that he will not return to his own time. He is soon confronted by Jose, an acquaintance from his own time, who gives Cole a handgun and instructions from the scientists to complete his mission. At the same time, Railly spots the true culprit behind the virus - Dr. Peters, an assistant at the Goines virology lab, who is carrying a briefcase full of vials, about to embark on a tour of the cities which Cole had earlier memorized as being the path of the viral outbreak. After fighting his way through security, Cole is fatally shot by police as he pulls a gun to stop Peters from boarding his plane. As Cole dies in Railly's arms, she makes eye contact with a small boy - the young James Cole witnessing his own death; the scene that will replay in his dreams for years to come.

Dr. Peters, safely aboard, sits down next to the lead scientist from the future. After some small talk with Peters, she introduces herself: "Jones is my name. I'm in insurance."

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