The story starts with the sudden disappearance of everybody aged 15 or older from the town of Perdido Beach, causing extreme confusion and chaos amongst those remaining in the town. Students Sam Temple, Quinn Gaither, Astrid Ellison, and Edilio Escobar discover an impermeable barrier cutting Perdido Beach off from the outside world; the area within the barrier is subsequently nicknamed "Fallout Alley Youth Zone", shortened to "the FAYZ". Unknown to the others, Sam had earlier discovered his superhuman ability to fire light from his hands capable of burning objects when he is afraid; after reading a journal entry by his mother Connie, a nurse at the nearby Coates Academy, Sam begins to suspect a connection to the disappearances and the barrier. While looking for Astrid's autistic four-year-old brother "Little" Pete at a nuclear power plant outside of town, the quartet discovers that the barrier's boundaries correspond to predicted radiation patterns in the case of a meltdown. Pete is revealed to have superhuman abilities in an incident where he chokes Sam, and that also exposes Sam's powers to the group, who agree to keep it secret.

Upon the group's return to Perdido Beach, they encounter vehicles bringing students from Coates Academy, led by the charismatic Caine Soren. Caine restores order to Perdido Beach with the aid of his confidante Diana Ladris and enforcer Drake Merwin, but Sam and Astrid are suspicious of Caine's motives. Caine (revealed to have the power of telekinesis), Diana (who has the ability to determine the strength of others' powers), and Drake (a violent sadist with no powers of his own) discover that when inhabitants of the FAYZ turn 15, they are confronted by something they desire before vanishing, a phenomenon nicknamed "the poof", but can remain in the FAYZ by resisting whatever tempts them. Caine also discovers that he and Sam are twin brothers that were separated at birth, with Sam remaining with their mother, a revelation that deeply upsets Caine. Quinn, who has started hanging out with Caine's friends, tells Caine of Sam's powers. Feeling threatened, Caine enlists his crew, including local bully Charles "Orc" Merriman and his lackey Howard Bassem, to kidnap Sam, Astrid (who has begun dating Sam) and Pete. Quinn frees Sam, and Astrid and Pete are freed from Drake by Pete's abilities. Caine instructs Drake to kill Astrid and Pete, but Sam saves her. Sam, Astrid, Quinn, Pete, and Edilio escape town.