The Chrysalids is set in a post-apocalyptic world hundreds of years after an unspecified, possibly nuclear disaster, known as Tribulation. 

The main character, David Strorm, lives on a large farm called Waknuk in a strictly religious Puritan community in rural Labrador, reminiscent of the American Frontier of the 19th century. The community ostracizes any plant, animal or human that shows any sign of genetic abnormality.

The story begins when David is nine years old and has a chance encounter with a slightly younger girl called Sophie, whom he helps home after she hurts her foot. He later befriends her and discovers she has six toes on her feet; he is entreated by her parents to keep it a secret.

David begins to realize the dangers of being different when Sophie and her family have to flee the district after her abnormality is accidently discovered. This becomes especially important to him when he discovers his ability to ‘speak’ telepathically with his cousin Rosalind: they too are different, despite appearing normal. Subsequently, he and Rosalind make contact with six other young telepaths in the surrounding area.

With the help of his Uncle Axel, David manages to keep his ability secret for several years, although it becomes difficult when his much younger sister Petra turns out to be an extremely strong telepath.

Things come to a head when Petra and her horse are attacked by a creature in the neighbouring woods and she summons David, Rosalind, and two of the other telepaths, Sally and Katherine, to help her. Unfortunately, the arrival of Sally and Katherine is witnessed by a local called Jerome Skinner who becomes suspicious.

Roused in the middle of the night with the news that Sally and Katherine have been arrested, David, Rosalind, and Petra flee to the Fringes, where all human mutants are exiled after first being sterilized.

They are hotly pursued by a posse that includes David’s father, and only manage to escape with the help of Michael, one of the other telepaths who joins the posse.

Increasingly desperate, Petra makes contact with a distant community of telepaths living in a country called 'Zealand' who offer to come to the rescue.

Sheltering with Sophie, who is living with the Fringes people and is in a sad state, David, Rosalind, and Petra are finally rescued by the Zealanders who arrive in a helicopter during the middle of a battle.