We start off with four army guys sitting around playing poker in 1959. It’s all fun and games until the lights start acting all crazy and... they all disappear. But why? And where did they go?
Meanwhile, in 2044, Katarina and Eckland, the boyfriend she forgot, seem to be getting pretty cozy in her quarters, kissing and playing cards. The moment however is interrupted when an alarm goes off indicating that someone is splintering in! It’s Cassie! Back from 2016 with some shocking news about her run in with The Witness. So shocking in fact that the team has a hard time believing her. Could Cassie really have seen The Witness, or was it just a hallucination brought on by that crazy tea the 12 Monkeys like so much? After a brief interrogation, Cassie decides it’s time to get some rest.
But of course — sleep eludes Cassie as she begins to hear some strange voices, which she follows to the splinter machine, where she sees The Witness tampering with the machine. But then Cassie wakes up back in her own room... we don’t know what to believe anymore. Meanwhile, Katarina decides to run some tests to see if there was any other temporal radiation with Cassie back in 2016, indicating another traveler is present somewhere. What she finds though is a phantom tether here in 2044! Could there be another traveler among them now? Before they can get any answers, the machine powers up and starts to go haywire, leaking temporal energy all over the place and all safety measures fail. This thing is gonna blow!
Everyone manages to escape the lab as the machine leaks more and more temporal radiation, but this radiation also seems to be bringing back some of Katarina’s original time travel test subjects, who are none to happy about being test splinters and are coming after Katarina for revenge. Also most of them have their organs on the outside. Which is gross. The team soon figures out that the machine has been sabotaged (by who?) and splits up. Cassie and Cole head to the core to shut it down manually but on the way there, they happen upon another of Katarina’s unfortunate test subjects. While Cole takes care of that, Cass vanishes. This does not bode well.
Meanwhile, Deacon and Dr. Eckland get a new lens from storage that will focus the temporal energy that is now bursting all over the place. They find the lens no problem, but when they try and bring it back to the lab, they bump into those Army dudes from 1959. These guys are very confused (and broy) about being in the future. Shots are fired but our boys from 2044 come out on top and are able to make it back to hopefully fix the machine. While all this is going on, Ramse and his son Sam are trying to make their way to figure out what the hell is going on when they meet up with an angry guard dog. As Ramse takes the dog out, a shadowy figure grabs Sam and leads him away.
Ramse and Cole meet up and decide that they need to shut down the core before searching for Sam, otherwise the thing will blow, killing them all. On the way to the core they see Sam. With Cassie. Great! Everything is gonna be fine, right? Wrong! Cassie leads Sam into the reactor and locks the door behind her. She seems to be being controlled by something else (The Witness?) and she does not want the guys to fix the core. While Cole and Ramse try and figure out what to do, Sam covertly directs them to another way into the room: the river under the floor.
Back by the time machine, it appears to be too late! The machine is way past the point of being able to repair it safely. If someone goes in to replace the lens now, they are goners. Before Katarina can stop him, Eckland goes in to fix it. He sacrifices himself so that the woman he loves, even though she doesn’t remember loving him, will be saved. And as soon as he fixes it, he’s gone. Feelings ensue.
Ramse and Cole make it into the room with Sam and Cassie and it is crystal clear that Cassie is 100% under the control of The Witness. There is no reasoning with her right now, so Cole decides that he has to do something drastic. Cole knows that there is no way that Cassie would ever let him die, so he tells him Ramse to shoot him. Ramse hesitantly obliges and just like that Cassie is back in control and comes to Cole’s side.
The team get control of the core a little too late though as it has already reached critical levels of temporal radiation and lets out one final burst in order to stabilize itself. Unfortunately, Sam is right there when it does and he is hit and disappears, splintering! To God knows where. Ramse, grieving for his son, decides to leave the facility. Cassie feels awful. This is all her fault. She was under the control of The Witness, yes, but technically it was her who sabotaged the machine. Katrina assures her that it wasn’t her fault and she will find a solution to all of this.
Cut to, who knows when? The years keep on flashing across the screen so we could be in anytime. But look! It’s Sam! He’s alive! And in the woods calling out for this dad but where/when are we? And who is the mysterious person who's there to greet him?
In this era, Raritan Laboratory is an army base. Four soldiers are sitting around playing cards, when suddenly they are splintered away without warning.
Railly continues to be haunted by visions of the Witness. She injects herself with her tether and splinters to 2044.
Jones and Eckland are in her bed, playing cards, when the alarm sounds.
Railly returns from 2016, continuing to see the Witness in her visions. She tells Jones and the rest of the team what she is seeing. She sees the Witness doing something to the time machine, then wakes up on the floor of her room. She speaks with Cole, who says he doesn't mind her friendship with Deacon. They agree that perhaps they don't know each other that well anymore.
Jones realizes a second, "phantom" tether entered the facility at the same time as Railly. The time machine malfunctions and is locked into permanent splinter mode. To prevent the machine from destroying the facility, Jones sends Deacon and Eckland to get a replacement lens for the time machine, while Cole and Railly try to shut down the power.
Suddenly, a horrifically deformed person appears and points a gun at Jones, before being shot down. Jones reveals that the man was once a test subject for Project: Splinter, and they deduce the machine is splintering people from random points in the timestream into the Temporal Facility.
Deacon and Eckland find the lens but run into two soldiers from 1959. When Deacon tells them they're in 2044, they start shooting. Initially, Eckland refuses to fight but ends up killing the soldiers with a grenade.
Jones says that the machine is breaking down and that anyone who tries to repair it will be exposed to lethal radiation. Eckland replaces the lens, sacrificing himself to save the facility in front of Jones's horrified eyes.
Cole loses track of Railly, and Ramse of Sam. Cole and Ramse run into each other and decide to go shut down the power. They see Railly with Sam. She locks herself and Sam into a room and points a gun at Sam's head. In a vision, she passes with Sam through the Red Forest and into the house on the hill, where a door is locked behind her, preventing her from escaping. She looks out a window and sees a water tower with the inscription "Titan," and the sigil of the Army of the 12 Monkeys.
Sam gestures to Ramse, who realizes that he is saying that an underground passage will allow them access to the room. Deacon arrives and helps Ramse get Cole into the room, despite the interference of two soldiers from 1959.
Cole realizes that the Witness is controlling Railly and manipulated her into sabotaging the time machine. He tries to reason with her, to no avail. Deacon tells Ramse he must get into the room and kill Railly to save Sam, since neither he himself nor Cole can do so. Once inside the room, Ramse points his gun at Railly. Cole has Ramse shoot him instead, saying the real Railly would never let him die. This allows her to break free of the Witness's control.
Ramse shuts down the power core, but a backlash of temporal energy strikes Sam and he splinters away. Ramse abandons Project Splinter and leaves on his own. Railly tends to Cole. Jones tells her the phantom tether was some kind of signal that allowed the Witness to control her. She gives Railly injections that will counter the effect of the red hallucinogen and prevent the Witness from influencing her mind. Jones says that Eckland's death and Sam's disappearance were both her fault, and resolves to set it right.
Sam finds himself in a forest where the red herb is growing. A hand is held out to him by a (unseen to the viewer) figure and he takes the hand and goes with them.