While on the run from the Army of the 12 Monkeys, Cole and Ramse repair their broken friendship. Meanwhile in 2043, Railly and Jones navigate an uncertain future as Deacon and the Twelve control the Temporal Facility.

When an attempt to destroy the virus changes the future, Cole finds himself stranded in 2016 with an unstable Jennifer Goines, who may or may not be his key to getting home.

Despite growing tension between them, Cole and Cassie embark on their first time travel mission together, splintering to New York at the height of World War II. In this sepia-drenched, bygone era, the pair track a dangerous member of the Twelve - a seductress who is on a mission of murder that could ultimately shatter time itself.

When Cole and Cassie are stranded in 1944, Jones must turn to the person she trusts the least to bring them home - Ramse.

In the present day, Cassie and Jennifer Goines are on the run from the 12 Monkeys in a desperate attempt to unravel the next part of the conspiracy. Meanwhile, in 2044, Cole and Ramse's conflict with Deacon comes to a head.

Cole's partnership with Ramse is put to the test when they travel to New York City of the 1970s to prevent the Twelve from murdering a disturbed Vietnam veteran with a connection to the Witness.

Cole comes face to face with the Witness, the phantom behind the Army of the 12 Monkeys as Cassie's hallucinations undergo a chilling evolution. Making matters worse, the Temporal Facility becomes increasingly dangerous after the malfunctioning time machine begins to tear apart time and space, bringing back deadly visitors from the past.

After the tragic events of the meltdown, Jones is left with the disheartening realization that humanity's true enemy is time-travel itself.

In 2016, Jennifer Goines has taken her power into her own hands and forms The Hyenas, a band of crazy compatriots, to take on the 12 Monkeys' organization.

Cole's loyalty is tested when Ramse and Railly go rogue and embark on an unsanctioned mission into 1961 East Berlin.

With the temporal facility on the verge of destruction, Cole and Jones find themselves in the middle of a coup.

Cole and Railly attempt to stop the final paradox in the past while Ramse, Jennifer and Deacon struggle to survive the apocalypse in a last ditch effort to find the Witness.

Cole and Railly have finally found peace living in the past.