New York City, 1965: Rosemary and Guy Woodhouse (Mia Farrow and John Cassavetes) are a young married couple who rent an apartment in the gothic and splendorous Bramford building in Manhattan. At first, their friend and current landlord Edward "Hutch" Hutchins (Maurice Evans) tries to dissuade them from doing so: the building has a rather unsavory past. It has been occupied by cannibal killers, Satanists and witches, such as the Trench Sisters, Keith Kennedy, Pearl Ames--and the sinister Adrian Marcato, who created a scandal in the late 1890s by claiming to have conjured "The Living Devil."
Rosemary and Guy ignore him and move in. Guy is an actor with a fledging career. He's done plenty of TV plays and commercials, which have made him good money; but he wants great parts. Rosemary is a gentle soul, originally from Omaha, Nebraska, where she had been raised in a Catholic home and had attended convent school.
As it is, Rosemary is estranged from her family, since they don't accept her marriage to Guy, who is not only an actor, but is also of mixed Jewish/Protestant upbringing. So her life in New York is all she has: she is a young housewife dedicated entirely to making a good home for her husband, whom she adores. She has a good circle of friends, but is at core sweetly naïve and lonely.
One day in the laundry room, Rosemary makes the acquaintance of Terry Gionnoffrio (Victoria Vetri), a young former drug addict who was "rescued from the gutter" by an elderly, eccentric couple, Roman and Minnie Castevet (Sidney Blackmer and Ruth Gordon). The Castavets's apartment had formerly been the front part of theirs, but is now separated by a partition.
Her friendship with Terry is short-lived. A few days after Rosemary meets her, Terry plunges to her death from the bay window. She and Guy are walking home when they see the police surrounding Terry's corpse. The Castavets happen to be walking home, too. Presumably distraught, they strike up an acquaintance with the Woodhouses and later invite them to dinner.
Soon, Rosemary finds that Minnie and Roman are, increasingly and unsubtly, becoming surrogate parents for her and Guy. And she doesn't like it. Other things trouble her, too. Guy's career got a jump start when his main rival, Donald Baumgart, suddenly went blind. Now all he cares about is his new play.
But then suddenly, he decides he wants to become a father. Rosemary is thrilled.
Evidently having studied her ovulation cycle himself, he announces the ideal "baby night." That evening, Minnie drops by to give them some chocolate mousse--or mouse as she calls it. Rosemary complains of a chalky undertaste, but Guy gets angry over her ingratitude. She eats part of it, and then furtively hides the rest in her napkin. Woozy from the wine--and, as we learn later, the "mouse"-- she passes out and has a bizarre dream. Rosemary visits the Sistine Chapel and sails on a cruise ship. The unsettling dream becomes a nightmare when two figures tie her to a bed. Something that looks and feel inhuman brutally rapes her. "This is not a dream!" she cries. "This is really happening!" Pope Paul VI, then visiting NYC and having mass at Yankee Stadium, comes to offer her absolution.
When she wakes up, Rosemary is sore and scratched. Guy half-heartedly apologizes for having had her while she was out. Rosemary is angry, but "baby night" later proves successful. Dr. C.C. Hill (Charles Grodin)--referred to her by her girlfriend Elise Dunstan (Emmaline Henry)--confirms it.
Upon hearing the news, the Castevets persuade Rosemary to go to Dr. Abraham Sapirstein (Ralph Bellamy), a prominent obstetrician who delivers all the upper crust babies in the city. Rosemary entrusts herself to him, accepting his odd advice and his recommendation of Minnie's strange "vitamin drinks." She develops pain during her first trimester, which causes her to lose weight and look emaciated, alarming Hutch--but not the doctor, Guy, the Castevets or their Saturday night gang of quaint old timers, including Dr. Stan Shand (Phil Leeds) and the obnoxious Laura-Louise McBurney (Patsy Kelly).
As her pregnancy progresses, Rosemary feels a mounting sense of dread and angst. What is wrong with her? Why won't anyone acknowledge it? She decides to throw a party for her young friends, a qualification she insists upon. Her girlfriends--including Elise, Joan Jellico (Marianne Gordon) and Tiger Hoanigsen (Wende Wagner)--tell her she looks awful and that her pain is far from normal. She has to see a new doctor. Rosemary tells Guy, and they fight bitterly over it. But at the last minute she relents. The pain has suddenly stopped. And now she can feel the baby kicking.
Near the end of her term, Hutch--who had inexplicably fallen into a coma a few weeks before--dies. But before doing so, he had asked his companion, Grace Cardiff (Hanna Landy) to deliver a book to Rosemary. It's called "All of Them Witches," a study on witchcraft through the ages, featuring a chapter on Adrian Marcato and his son, Steven.
"The name is an anagram," is the final clue Hutch had left for her. Rosemary uses her Scrabble tiles to learn the horrible truth: Roman Castevet is Steven Marcato.
Now she suspects Roman, Minnie and all their all-too-helpful friends are Satan worshipers. She visits Dr. Sapirstein and tells him she'll have no more to do with them. It's just as well, Sapirstein informs her: Roman is dying and would like to go away to Europe on a farewell tour. Rosie feels guilty about her suspicions, and when the time comes, bids them a fond farewell.
But not all is what it seems. As her due date--June 28, 1966--nears, she learns one strange thing after the other. Could it be that Guy is involved with witches? Witches use babies for their rituals. Has he promised them the baby?
She learns that witches use the belongings of their intended victims to blind or kill them. Guy had exchanged ties with Donald Baumgart. Is that how he went blind? Hutch lost a glove the last time he had visited. Is that how he went into a coma and later died? Did her neighbors and husband use these things to cast spells upon them?
She packs a suitcase and goes to Dr. Sapirstein to tell him what she's learned. But his secretary's off-hand remark reveals something horrible--the good doctor sometimes smells like tannis root, which she has learned is more commonly called Devil's Pepper. Dr. Sapirstein is a witch, too. He must be part of the plot against her.
Next, she persuades Dr. Hill to see her. But he only pretends to take her seriously. She falls asleep in his office when Guy and Dr. Sapirstein arrive to take her back home. She manages to trick them and lock them out of the apartment. But her effort was futile. The closet conceals a passageway from the Castavets' to her apartment. The entire coven arrives to reassure her that everything will be all right.
She knows better. They have to force her down on her bed, while Sapirstein injects her with something to make her sleep. She's also in labor.
When she wakes, Guy tells her she has had a boy and that he's fine. But later the baby dies--or so says Sapirstein. Rosemary doesn't believe it. She knows they have taken the baby and are planning to sacrifice it for one of their rituals.
But the horrible truth proves to be not what the coven plans to do with the baby--but what the baby is. Rosemary's baby is the son of Satan.