A deadly virus, released in 1996, wipes out almost all of humanity, forcing survivors to live underground. A group known as the Army of the Twelve Monkeys is believed to have released the virus.
In 2035, James Cole is a prisoner living in an underground compound beneath Philadelphia. Cole is selected to be sent back in time to find the original virus to help scientists develop a cure. Meanwhile, Cole is troubled by dreams involving a foot chase and shooting at an airport.
Cole arrives in Baltimore, 1990, not 1996 as planned; he is arrested and incarcerated at a mental hospital on the diagnosis of Dr. Kathryn Railly. There he encounters Jeffrey Goines, a mental patient with environmentalist and anti-corporatist views. Cole is interviewed by a panel of doctors where he tries to explain that the virus outbreak has already happened.
After an escape attempt, Cole is sedated and locked in a cell, but he disappears, waking up back in 2035. Cole is interrogated by the scientists who play a distorted voicemail message that asserts the association of the Army of the Twelve Monkeys with the virus. He is also shown photos of numerous people suspected of being involved, including Goines. The scientists offer Cole another chance to complete his mission and send him back in time. Cole accidentally arrives at a battlefield during World War I, is shot in the leg and then transported to 1996.
In 1996, Railly gives a lecture about the Cassandra complex to a group of scientists. At the post-lecture book signing, Railly meets Dr. Peters who tells her that apocalypse alarmists represent the sane vision while humanity's gradual destruction of the environment is the real lunacy.
Cole arrives at the venue after seeing flyers publicizing it and, when Railly departs, he kidnaps her and forces her to take him to Philadelphia. They learn that Goines is the founder of the Army of the Twelve Monkeys before they set out in search of him. When Cole confronts Goines, he denies any involvement with the group and says that, in 1990, Cole originated the idea of wiping out humanity with a virus stolen from Goines' virologist father, Dr. Leland Goines.
Cole is transported back to 2035 where he reaffirms to the scientists his commitment to his mission. But when he finds Railly again in 1996, he tells her he now believes himself crazy as she had suggested. Meanwhile, Railly has discovered evidence of his time travel which she shows him, believing he is sane. They decide to depart for the Florida Keys before the onset of the plague.
They learn that the Army of the Twelve Monkeys was not the source of the epidemic; the group's major act of protest is releasing animals from a zoo and placing Goines' father in an animal cage. At the airport, Cole leaves a message telling the scientists that following the Army of the Twelve Monkeys is the wrong track and he will not return. Cole is confronted by Jose, his cell mate from his own time, who gives Cole a handgun and instructs him to follow orders.
Railly spots Dr. Peters at the airport and recognizes him from a newspaper as an assistant of Goines' father. Peters is about to embark on a tour of several cities that match the locations of the viral outbreaks.
Cole forces his way through a security checkpoint in pursuit of Peters. After drawing the gun he was given, Cole is shot by police. As Cole lies dying in Railly's arms, Railly suddenly begins to scan the crowd around her. Railly finally makes eye contact with a small boy—the young James Cole witnessing the scene of his own death, which will replay in his dreams for years to come. Peters, aboard the plane with the virus, sits down next to Jones, one of the scientists from the future, who comments that her job is "insurance." The young Cole watches the plane take off from the ground outside the airport.
Bruce Willis as James Cole
Joseph Melito as young James Cole
Madeleine Stowe as Dr. Kathryn Railly
Brad Pitt as Jeffrey Goines
Christopher Plummer as Dr. Leland Goines
David Morse as Dr. Peters
Jon Seda as Jose
Christopher Meloni as Lt. Halperin
Frank Gorshin as Dr. Fletcher
Vernon Campbell as Tiny
Lisa Gay Hamilton as Teddy
Bob Adrian as Geologist
Simon Jones as Zoologist
Carol Florence as Astrophysicist/Jones
Bill Raymond as Microbiologist
Annie Golden as Woman Cabbie
Thomas Roy as a street preacher
inspired by Chris Marker's 1962 short film La Jetée