Cole gets stranded in 2016 after an attempt to destroy the virus changes the future. Jones and Railly deal with the consequences of the changed timeline.

Despite the growing tension between them, Cole and Cassie time travel to New York during World War II to track down a dangerous member of the Twelve.

When Cole and Cassie are stranded in 1944, Jones must turn to the person she trusts the least to bring them home -- Ramse. For Ramse, this mission will give him a chance to atone for his sins -- but can he mend the broken relations between Cole and Railly? Meanwhile, Jones visits Old Jennifer Goines to explore the true nature of Time - and the Twelve’s method to destroy it.

In the present, Cassie and Jennifer Goines run from the 12 Monkeys; in 2044, Cole and Ramse face off against Deacon.

Cole and Ramse travel to 1970s New York City to prevent the Twelve from murdering a Vietnam veteran with a connection to the Witness.

Cole faces the Witness as Cassie's hallucinations evolve; deadly visitors from the past arrive when the time machine malfunctions and begins tearing apart time and space.