In 1996, the Earth fell victim to a monstrous epidemic, and the survivors had to hide underground to remain alive, where a rigorous government began to look for a solution. 30 later years, James Cole is selected to be sent back into the past, and to inquire about the initial propagation of the virus.
Time voyage techniques haven't yet been perfectly mastered, James is not sent to the correct period the first time, but 6 years before. He meets Jeffrey, a psychiatric asylum companion, and Kathryn Railly, a psychoanalyst, and he tells them about the "12 monkeys" army, an organisation that should have existed at the beginning of the epidemic. After a brief return to his own time, James goes back in time once more, to 1996.
Strongly disturbed, he doubts his own sanity, and attempts to convince himself that this epidemic and time travel are only ghostly hallucinations.
Besides Kathryn, who he succeeded in convincing about the danger, he discovers the real nature of the 12 monkeys's army, of which the famous Jeffrey seems to be a protagonist. Gamble or cause ?