Mike Howell (Jesse Eisenberg) is in a holding cell, handcuffed and trembling. A man enters the room while another (Bill Pullman) watches them. Mike sees flashes of the last few days, as well as items such as a bloody spoon, a frying pan, and a shot-up teddy bear.
Three days earlier, Mike was living peacefully in Liman, West Virginia with his girlfriend Phoebe (Kristen Stewart). He's a stoner and he is head-over-heels in love with Phoebe. Mike planned a surprise trip to Hawaii for the two of them where he hoped to propose to her, but they missed their flight because he was having a panic attack in the bathroom. Mike apologizes to Phoebe repeatedly but she forgives him.
Mike returns to his dead-end job as a clerk at the local convenience store. Since business is slow, he kills time by drawing cartoons and rolling joints.
At the CIA Headquarters, Victoria Lasseter (Connie Britton) is going through classified files when her former assistant Petey Douglas (Tony Hale) enters. She then gets a phone call from a disguised voice saying "Tough Guy" is moving in on the "Little Man". She confronts another agent, Adrian Yates (Topher Grace), as they both know this involves Mike and his association with a program that Victoria started, the Ultra Program. Yates wants Mike dead immediately and orders Victoria to leave.
Mike and Phoebe are sharing a joint at a spot overlooking a street where they see a bunch of cop cars and a tow truck taking a car that crashed into a tree. A very stoned Mike talks about how the tree has just been standing there forever and only just did something by stopping the car. He starts crying because he thinks he's the tree and Phoebe is the car. She comforts him and says that's not the case.
The next day, Mike meets his buddy Rose (John Leguizamo) to get fireworks, as he wants to propose to Phoebe using them.
Later that night at work, Victoria approaches Mike with a soup cup and a milk bottle, and she speaks in codes. He has no idea what she means, and she leaves frustrated. Mike goes outside to smoke a joint and eat the soup when he sees two guys putting something on the tires of his car. He calls to them, and they approach him with knives. Something in Mike goes off and he quickly reacts by throwing the hot soup in one guy's face before disarming both of them. He stabs the other guy in the neck with a spoon and then shoots both goons dead. Freaked out, he calls Phoebe at work. She rushes over and sees the dead men. They're then both arrested by the sheriff that already knows both of them.
Yates gets wind of what happened and knows that the codes Victoria said to Mike were meant to activate his skills. He orders two of his own agents, Crane (Monique Ganderton) and Laugher (Walton Goggins) to find Mike and Phoebe at the station, as well as a whole lockdown of the town. Crane opens fire and kills the officers while Laugher goes to kill Mike himself. Mike and Phoebe fight him and lock him in the cell. They escape the gunfire, but Crane calls to Mike and throws him a grenade. He catches it and throws it back, blowing up the station. He then runs to Crane and punches her a few times before breaking her neck.
Mike and Phoebe head back to the store where Mike left his car. He freaks out again and they hug each other. The wind blows a bag onto Mike's car, setting off a bomb that the goons from earlier planted on the car.
Yates is brought to a truck full of sleeper agents, including Laugher, who survived the explosion at the station. Yates decides to use him and a few others to go after Mike.
The two take Phoebe's car to Rose's home where they can be protected. Rose is suspicious when he sees them because the news is making it seem like Mike contracted typhoid from Victoria, and that's why the town is on lockdown.
Meanwhile, Victoria comes across the station and sees Crane's corpse sitting outside. She contacts Petey and asks for his help. He sends her a package containing guns and files on Crane and Laugher. Victoria realizes that Yates is using people with mental health problems as part of his program. She talks to Petey, who says he can't help her because he's been told she is committing treason.
A few sleeper agents sneak around Rose's home and spread a poisonous gas through the vents. Another agent breaks in and kills Rose and his two buddies while Mike and Phoebe are in the next room. Phoebe tries escaping through the ceiling but falls through as one agent attacks Mike. Mike is exposed to the gas but he rips the mask off the agent, which Phoebe takes. Mike bashes the agent's head in with a weight and slowly slips out of consciousness.
Phoebe grabs Mike and takes him outside. She kills the agent that let the gas in and takes an antidote from him, then injects it into Mike. He feels sleepy but Phoebe warns him that he will die if he slips away. Mike then sees flashes of nothing but his time with Phoebe as she pleads with him to wake up. He pukes and is okay but asks Phoebe how she knew what the gas was. She then admits that she is CIA and has been his handled for the last five years. Betrayed, Mike retreats to her car. She runs there with him, and the car is then hit by Laugher, driving in a larger vehicle. The car falls over a bridge. Laugher grabs Phoebe and pours gas all over the car. Victoria shows up and gets Mike out before Laugher lights it up and makes the car explode. He takes Phoebe back to Yates.
Victoria takes Mike somewhere safe and tells him that he volunteered at a young age for the Ultra program after getting in and out of trouble a number of times. She erased his memories and gave him phobias to prevent him from leaving home. They return to Mike's house where he would rather die stoned.
Three more agents arrive and shoot at Mike. At the same time, Yates orders Petey to send out a drone to blow up Mike's home. Victoria kills one using a teddy bear as a silencer. Mike kills another and then finishes the last by bouncing a bullet off a frying pan. Petey cancels the drone strike to spite Yates. He then calls Raymond Krueger (the man watching Mike at the beginning).
Mike gets in touch with Yates and arranges to get Phoebe back at a nearby supermarket. There, Yates brings Phoebe with a bunch of other assassins. Mike uses the fireworks as he makes his entrance, driving through the store. He takes on all the assassins, killing them with whatever he can get his hands on in the store (a meat cleaver and hammer, for instance). He is left to face Laugher while Yates takes Phoebe with him. She uncuffs herself with a paper clip and punches Yates in the face. Victoria then catches him and nearly strangles him to death with a cable until Krueger arrives and stops her. Mike almost finishes off Laugher until he slumps over and apologizes, saying he can't control what he does, and that Mike is a better agent than him.
Mike finds Phoebe and they walk outside together to face the SWAT team and other armed troopers. Mike takes this opportunity to propose to Phoebe. She says yes but the moment is killed when both of them get tased.
Krueger takes both Yates and Victoria into the woods and reprimands them for letting all the deaths happen as a result of getting Mike activated. Krueger shoots and kills Yates, and nearly does so with Victoria until she convinces him that Mike is a very valuable asset.
Six months later, Mike and Phoebe are in the Philippines on what appears to be a romantic getaway. Mike leaves Phoebe at the front desk, and she looks into a camera where Victoria and Petey are watching them. Mike gets into an elevator and is taken by two Mandarin gangsters, as planned by Victoria. The main gangster threatens and taunts Mike, but Mike observes what he can get his hands on in the room and he springs into action.
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