Rosemary and Guy Woodhouse, a young married couple, move into the Bramford, an old Manhattan apartment building said to have a sinister past. Their elderly neighbours, Minnie and Roman Castevet, befriend them. A young woman staying with the Castevets falls to her death from their window, apparently a suicide, and the couple grows closer to the older pair.
Guy spends more and more time with the Castevets, and his acting career suddenly takes off when a rival actor mysteriously goes blind. Guy and Rosemary plan to have a baby. On the night they planned, Rosemary is given a dessert from Minnie and passes out. She experiences a horrifying, dream-like assault by a monstrous creature, surrounded by naked elderly people. Guy says he had sex with her while she was unconscious.
Rosemary becomes pregnant. The Castevets send her to their friend, the famous obstetrician Dr. Sapirstein, who gives her daily herbal drinks made by Minnie. Rosemary suffers terrible pain and loses weight. Her old friend Hutch becomes worried and starts researching the building's past, but falls into a coma and dies. Before dying, he leaves Rosemary a book about witchcraft, with the message "All of them witches".
Using a Scrabble set, Rosemary discovers that Roman Castevet is an anagram of Steven Marcato, the son of a notorious Satanist. She becomes convinced the Castevets, Dr. Sapirstein and even Guy belong to a coven that wants her baby for a ritual. She tries to escape to another doctor, but he hands her back to Guy and Sapirstein.
Rosemary is sedated as she goes into labour. When she wakes, she is told the baby died. But she hears a baby crying through the walls, and finds a hidden passage into the Castevets' apartment. There, the coven is gathered around a black cradle. Rosemary looks inside and is horrified: the baby is the son of Satan. Roman urges her to be the child's mother. After a moment, Rosemary begins gently rocking the cradle.
