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) on a trip to Hawaii however due to a fear of travel he is unable to board the plane. It is revealed he has had similar issues trying to leave town in the past and does not understand why Phoebe is so nice about it. 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 erased memory, 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 and follows through, 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. On the way there Mike becomes increasingly unnerved by an array of “new” facts he knows regarding military strategy. He also realises he has very little memory regarding his past prior to living in the town other than his name and Phoebe and wonders aloud why he never thinks of these things.
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 house 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.