It's 2043 and our hero, Cole, is preparing to go back in time to 2013 to enlist the help of Dr. Cassandra Railly in locating the creator of a virus.
The desperate time traveler kidnaps Cassie and begins to explain his mission. "About 4 years from now, most of the human race is gonna be wiped out by a plague; a virus. All we know is that it's because of a man named Leyland Frost."
By killing this man and rewriting history, Cole's team believes the plague will never happen.
Naturally, Cassie thinks he's got a few screws loose. However, Cole hands her an exact duplicate of her watch only it's from his time. He scratches the glass with a knife and Cassie's watch is instantly scratched too.
Several police cars catch up with them, and Cole is wounded but before vanishing he asks Cassie to meet him in 2 years in Philadelphia.
After the watch trick and witnessing Cole vanish before her eyes, she believes him and heads to the hotel to wait for Cole to appear in 2015. When he finally arrives, Cassie realizes he is still sporting the gunshot wound.
Cole is pleased that Cassie believes him, so he shares the story of the 2017 pandemic which claimed 7 billion lives. Luckily he was one of the rare few who were immune. These survivors became scavengers and took advantage of the chaos to survive.
Cassie learns she died in his time, but she was able to send a message mentioning Cole by name. "You gave me this mission. You're the reason I'm here" Cole tells her.
Unfortunately two years had passed, but Cassie still had no idea who Leland Frost was. However, a friend from the NSA tracked down a man named Leland Goines. His security ID was Frost, thus the confusion.
The duo are told their target will be attending a big Washington DC benefit. This was the perfect opportunity for Cole to take him out.
Our hero attempts to kill Goines but fails and is captured by the man's security team.
The old man tells Cole that they met previously in 1987 and he looked exactly the same. He remembered Cole mentioned the army of the 12 Monkeys back in '87 claiming they were responsible for the virus.
In an effort to escape, Cole offers to show Goines a neat trick. He touches Cassie's present and future watch together causing time to slow down for him. Cole throws Cassie over his shoulder and runs out of the room before the paradox causes the watches to explode.
He and Cassie manage to escape the blast, but Goines escapes as well. Cole returns to finish Leland Goines off with a bullet to the head.
Yes, Goines was dead but Cole was still there... he had not been erased. Why?
The mission had failed, but armed with this new knowledge of the 12 Monkeys, Cole returns to 2043.
He tells his team everything that took place and that the true architects of the plague are these 12 Monkeys.
Elsewhere, Goines' daughter is told that her father is dead and she has inherited his entire fortune but Jennifer is too busy drawing monkeys on the wall to care.