Chronologically, the series starts with the fourth novel published, Wild Seed. Set in the 17th and 18th centuries, the story involves the relationship between two immortals - Doro, a man born in Africa thousands of years ago, who survives by transferring his consciousness from one body to another (feeding on each new victim's mental energy in the process), and Anyanwu, a shape-shifter with perfect control over her body. They struggle to live together over generations as Doro attempts to create a new race through a selective breeding program.
Mind of my mind
The series' history continues with Mind of My Mind, in which Doro's breeding program has created a society of networked telepaths that he struggles to control.
Clay's Ark, the last book of the series to be published, deals with a colony of people who have been mutated by a disease that astronauts brought back to Earth from outer space. The group struggles to keep itself isolated enough to keep the disease from spreading throughout humanity.
Survivor, the book in the series that Butler later disowned, depicts the Clay's Ark disease ravaging the Earth, and Doro's telepathic descendants asserting control over what remains of humanity. One group of regular humans decides to escape Earth to a new planet, where they struggle to co-exist with the species that already lives there.
Patternmaster, the first book to be published but the last in the series' internal chronology, depicts a distant future where the human race has been sharply divided into the dominant Patternists, their enemies the "diseased" and animalistic Clayarks, and the enslaved mutes. The Patternists, bred for intelligence and psychic abilities, are networked telepaths. They are ruled by the most powerful telepath, known as the Patternmaster. Patternmaster tells the coming-of-age story of Teray, a young Patternist who learns he is a son of the Patternmaster. Teray fights for position within Patternist society and eventually for the role of Patternmaster. Patternmaster explores the creation and maintenance of social and genetic hierarchies. For Gregory Jerome Hamton, Patternmaster "presents several questions about how race works in a social structure and how gender works in the function of race."