Fourteen-year-old Maximum Ride (Max) is on the run with the other members of her "flock," which include Fang and Iggy (also 14); Nudge (11); Gasman (8) and Angel (6.) Previously they escaped from a lab they call the School, where they were given wings and other special powers. The scientists at the School also developed creatures called "Erasers," human-wolf hybrids that are hunting the flock in hopes of returning them to the lab. When the Erasers track down the flock, Max and her friends are shocked to learn the Erasers have been given wings. The wings are unwieldy for the Erasers, and the flock easily outmaneuvers them. Max also discovers that Ari, the leader of the Erasers, is still alive. She believed she had killed him in an earlier fight. During that fight, she had also learned that Ari is her brother.
Fang is seriously injured in the battle with the Erasers and has to go to a hospital. The FBI investigates the bizarre case of human-avian children; the government has heard of the School. The children evade answering any of the agents' questions. Another agent, Anne Walker, informs Max that if the flock will allow the agents to examine them, they will protect the children in a safe house, giving Fang time to recover and the others a chance to rest and eat regular meals. Max agrees, and once Fang is able to travel, they move into Anne's house, located in rural northern Virginia.
The flock settles into life with Anne. Soon after, Max begins having strange visions where she sees herself morphing into an Eraser. She also experiences hot flashes. She keeps her worries to herself as the other children are finally beginning to have fun. Slowly Fang recovers from his wound. Fang approaches Max with his theory that the coded information they'd stolen earlier from a place called the Institute might be map coordinates of where each child in the flock originated. Max and Fang find the locations while the rest of the flock sleep. The first two coordinates turn up nothing, but at the third, they find a picture of a baby who looks like Gasman.
The next morning, Max has another vision in which she turns into an Eraser. Max makes Fang promise to take care of the flock if she ever turns bad. That night the flock takes a midnight flight. Max discovers that the heat flashes are actually a sign that she can now reach incredible new speeds while flying. Meanwhile, her brother, Ari, keeps the flock under surveillance and looks for another opportunity to capture Max.
Anne enrolls the children in a private school where they all struggle to fit in. It's a difficult transition as they've never had to blend in with normal kids. Gasman and Iggy sneak off during recess to explore the school's basement. They overhear the headmaster telling a teacher to hide some old files so they can't be found by anyone else. That night Max catches a news piece about missing children. When she looks closely at the mother on TV, she realizes the woman looks just like Iggy. The woman's last name is the same as Iggy's, and her baby was stolen 14 years earlier.
Max goes on her first date with a classmate named Sam. After seeing a movie, they stop to get ice cream. Max is distracted when she sees Ari outside the window. Before Max can flee, Ari walks away, but Max glimpses a girl, who could be her twin, leaving with him. That night she confides in Fang, telling him about the visions she's had and the glimpse she caught of her twin with Ari. Fang assures her that she'll never turn into an Eraser and that he would be able to tell if a mutant, evil Max ever showed up to take her place.
Max and the flock get suspicious of the school they're attending after learning it's only been in existence for two years, even though a plaque says it was established in 1985. They agree to be careful and prepare to leave Anne's soon. Max and Fang tell the others that they've located Iggy's parents. Iggy decides he wants to be reunited with them. The flock goes with him, and the couple verifies Iggy is their son by his birthmark. He stays with them.
Anne is worried about Iggy's disappearance and tries to get the others to say where Iggy has gone, but they won't, even when she threatens to call the police. A special assembly is called at the school to tell the other students that Iggy is missing. When Max runs into the teachers' lounge to escape the prying questions of her classmates, she discovers that some of the teachers are carrying Tasers. Max and her flock escape. They fly back to Anne's to pick up their pet dog, only to discover the yard crawling with Erasers. After saving the dog and sending the rest of the flock to safety, Max confronts Anne and Jeb, the man who created her. Jeb tells Max that Anne is his boss, the woman pulling all the strings on the project. Max escapes, followed by Ari, who no longer wants to kill her, but wants to cut off her wings and keep her as a prisoner in a place where only he can talk to her. Fang helps her escape from Ari and together they rendezvous with the rest of the flock, including Iggy, who has returned after his parents discovered his mutations and wanted to sell his story to the tabloids.
Max and the others fly to Florida. Angel has read the minds of some of their former teachers. They think Max is supposed to help save the world from some kind of apocalypse caused by Itex, an international conglomerate with divisions in all kinds of technologies. After a brief detour to Disney World, the flock makes their way to the town where Itex is headquartered. They spend the night in a motel. There, Max is kidnapped, and her double is left in her place. Max is kept in an isolation tank, which is tortuous to her. Jeb manages to rescue her for a brief moment. He tells her that Itex wants to kill her and put in her replacement because they think she's too soft to save the world. Max is thrown back into the isolation tank, while her counterpart, pretending to sneak the flock into Itex headquarters, leads the flock into an ambush.
Once in Itex, Nudge manages to call up information about the human-avian program on the Itex computer, including details on how she was kidnapped and created. Even Max's evil twin is surprised to see that Jeb's signature is on the order sheets.
The real Max slows down her body functions in order to trick her captors into thinking she's dead. The plan works, and she escapes when they pull her out of the tank to examine her. She finds her way to Itex and confronts her counterpart. The two battle while the flock and a group of scientists, including Jeb, watch. When the real Max gets the upper hand, she starts to choke her twin, but in the end, Max allows her to go free because she doesn't want to sink to the level of the scientists. An explosion incapacitates the scientists and gives the flock an opportunity to escape.