The following version of the book was used to create this study guide: Power, Rory. Wilder Girls. Random House, LLC, New York, New York, 2019. Kindle AZW file.

Hetty, Byatt, and Reese were students at a boarding school, located on Raxter Island off the coast of Maine. A strange disease is spreading through the student body, infecting everyone in different and grotesque ways and killing many. The students have been living amid the disease for over a year. They have settled into a semblance of routine, given their terrible situation. Not only have the girls changed, but the island's fauna and animals have changed as well, meaning the land is especially dangerous outside the fenced campus. There is an enormous bear, the deer have become carnivores, and the trees have grown bigger than usual. The Navy brings supplies to a dock at the opposite end of the island and a teacher, Miss Welch, leads a group of three girls to pick up the supplies. When one of them announces she is no longer willing to be part of the group, Miss Welch chooses Hetty to become one of the Boat Girls.

During the first trek across the island, Hetty gets her first look outside the fence in almost two years. She is amazed at the amount of food waiting for them on the dock and is horrified when Miss Welch throws most of it away. What Hetty does not realize until much later is that Miss Welch is doing her best to protect the girls from experiments. The Navy has tampered with much of the food, leaving the girls with only very basic rations and never enough to fill up the almost 60 hungry girls still alive at the school. At this point, Hetty only feels shame that she and the others bring back a small portion of the food.

The Tox is different for each person. One of Hetty's eyes has closed over and she can feel something moving around behind the fused eyelid. Byatt has developed a second spine that stands out against her skin. Reese has a webbed hand that is scaled over with hard, spiky scales. The other girls have various changes, ranging from an extra heart that is beating away in the chest of one girl to vicious bruises that simply appear and never fade. The girls sometimes experience flare-ups that leave them with new abnormalities and sometimes kill them, so no one is surprised when Byatt falls victim. Miss Welch takes her away and Hetty soon realizes that Byatt is no longer at the school. Byatt has been taken to the visitor center at the other end of the island where she fools a young orderly into kissing her, giving him the disease and killing him in the process. That, combined with the fact that Hetty and Reese left the school grounds without permission, prompts the decision to abandon the island, killing those left alive and bombing it.

Doctors give Byatt a fatal dose of poison but Byatt, finding something the doctors had missed, discovers a parasite in her arm and she digs it out. Without the parasite, the poison proves less effective and she manages to make her way outside where she plans to die. Before they leave the school campus, Hetty and Reese also discover that the Headmistress knew there was something wrong on the island but chose to expose the girls anyway. The Headmistress had planned to leave them all to die but Hetty and Reese spoil that plan.

Reese knows the island well because she grew up here. Her father has worked as caretaker. He is the only man who lives on the island. He has a house near the school campus. Reese knows where a small motor boat is stashed on the shore, but she has refused to consider leaving because she hopes that her father is still alive, somewhere on the island. When that hope is dashed, Reese gives in to Hetty's desperation to find Byatt. So, the girls take the boat. They notice an isolation tent has been pitched over the visitor center near the dock and realize that the military would not have risked taking Byatt off the island. They find Byatt outside and are shocked to discover she is alive, though barely. Hetty refuses to leave Byatt behind and Reese, who has loved Hetty since the first time they met, helps get them in the boat. As the novel ends, the three girls are waiting for the tide to change so they can reach the mainland. They have a vague plan to find Hetty's father, who is in the Navy, in the hope of prompting officials to find a cure.