Mike Howell (Jesse Eisenberg) is a stoner who lives in the sleepy town of Liman, West Virginia, where he works as a convenience store clerk, and is planning to propose to his longtime girlfriend, Phoebe Larson (Kristen Stewart). Meanwhile, in Langley, Virginia, CIA agent Victoria Lasseter (Connie Britton) learns that Mike, the sole survivor of her unsuccessful Ultra program is to be eliminated by her rival, Adrian Yates (Topher Grace), whose Tough Guy project succeeded where hers failed. Feeling that she has a duty to protect Mike, Lasseter travels to Liman and "activates" Mike through a series of code words. Because of his excessive drug use, Mike fails to understand their significance, and she leaves in resigned frustration.
Mike finds two of Yates' men planting a bomb in his car and is attacked, but his training allows him to quickly overpower and kill them. Horrified, he calls Phoebe, who reunites with him just as they're arrested for the apparent murders. Yates sends two Tough Guy operatives, Laugher (Walton Goggins) and Crane (Monique Ganderton), to kill Mike and Phoebe at the police station, but they evade Laugher and kill Crane before escaping to the apartment of Mike's drug dealing friend Rose (John Leguizamo), who begrudgingly hides them. Yates places the city under quarantine, and puts Lasseter and Mike's pictures on the local news. Lasseter contacts her former assistant, Petey Douglas (Tony Hale), to send her a weapon that she can use to defend herself and Mike. Yates finds out and threatens Petey with charges of treason, causing Lasseter to be denied further help. Yates then attacks Rose's apartment with three agents using a lethal gas. The agents kill Rose and his two guards, while Phoebe rescues Mike from the gas, which she is familiar with. When pressed for answers on her knowledge of the gas, Phoebe reluctantly reveals she was a CIA agent assigned to be Mike's handler, leaving him heartbroken.
Laugher ambushes the duo and captures Phoebe. Mike is rescued by Lasseter and brought back to his house. He then learns that he volunteered for the Ultra Program due to his criminal record and subsequently had his memories erased. He also learns that Phoebe's original mission was to get him settled in Liman and then leave, but chose to stay because she legitimately fell in love with him. Yates' men locate him, but Mike and Lasseter fight them off, prompting Yates to order a drone strike on the area. Petey refuses to follow his orders and secretly reports the situation to Yates' superior, Raymond Krueger (Bill Pullman). Mike contacts Yates and arranges to exchange himself for Phoebe. He sets off a series of fireworks and dispatches all of Yates' men before fighting and defeating Laugher, who is spared when Mike learns he is a mentally unbalanced man forcibly conscripted to Yates' Tough Guy program. Yates attempts to flee with Phoebe, but she escapes, while Yates is caught by Lasseter and nearly killed before Krueger intervenes and stops her.
Mike finds Phoebe and proposes to her at gunpoint before State Troopers/Sheriffs. While in a forest in the rain Krueger talks to Yates and Lasseter, both kneeling and placed in bonds. Yates argues that what he was doing would have been ok with Krueger if the results had been successful . Krueger admits that he would have approved of what Yates had done if the results were successful. Yates, believing his is being spared, stands and is executed by Krueger. Lasseter convinces Krueger to spare her life and Mike's by pointing out that, by taking out all of Yates' agents, he demonstrated he was both a valuable asset and that the Ultra program was already successful. Six months later, Mike and Phoebe are in the Philippines, agents on assignment, quite happy and confident now that they know who they are.