Alexandra Medford (Cher), Jane Spofford (Susan Sarandon), and Sukie Ridgemont (Michelle Pfeiffer) are three dissatisfied women living in the picturesque town of Eastwick, New England. Alexandra is a sculptress and single mother of one daughter, Jane is a newly divorced music teacher incapable of having children, and Sukie is an extremely fertile woman with six daughters, who also works as a journalist at the "Eastwick Word". Besides an everlasting friendship, these three women also share the similar misfortune of being abandoned by their husbands. Unaware that they are witches, the women unwittingly form a coven, of which they have weekly get-togethers, where they share their fantasies about ideal men.
The day after one such gathering, a mysterious man (Jack Nicholson) arrives in the town and immediately stirs up trouble by buying the city's landmark property, The Lennox Mansion. The arrival of this enigmatic stranger causes fascination among the townsfolk, all except local townswoman Felicia Alden (Veronica Cartwright), the Christian wife of newspaper editor Clyde Alden (Richard Jenkins). Clyde is also the boss of Sukie', whom Felicia dislikes. Although Felicia is not a witch, she is somehow able to sense that this man, whose name is easily forgotten, is up to no good. One night, at one of Jane's music recitals, the strange man appears and makes a spectacle of himself, which leads to more gossip among the people. After the recital, Jane receives flowers and a personal note from the man with the initial "D" written on it. This sparks Sukie's memory, finally revealing the man's name as Daryl Van Horne. At the very moment Sukie’s recollection, her beaded necklace inexplicably breaks and falls to the floor, causing Felicia, who mocked Daryl's name, to trip down a large staircase and break her leg.
Not long after his arrival, Daryl begins to seduce the women one by one, beginning with self-assured Alexandra, who is at first appalled by Daryl’s arrogance and bravado, but later falls in love. After making love to Alex, Daryl moves on to his next victim, Jane, who is considered very insecure and shy. As the two sit down and share polite conversations, Jane explains to Daryl that The Lennox Mansion was once the area where people were persecuted after being accused of witchcraft. Daryl soon begins to encourage Jane to stop living a life of doubt and learn to enjoy herself by living recklessly. Taking his advice to heart, Jane begins living carelessly by letting her hair down and indulging into alcohol and sex. The next day, Daryl invites all three women over to the mansion, which allows him to finally turn his attention onto Sukie. Envy and rivalry emerges among the women, leading to a supernatural game of tennis, causing the tennis ball to telekinetically decrease its speed. Finally aware of their magical abilities, the women spend more and more time with Daryl, agreeing to share him. As the women continue their presence at Daryl's mansion, Felicia begins spreading rumors about the three women’s indecency. Due to the gossip and public opinions extending throughout the town, Alexandra, Jane, and Sukie become the outcasts of Eastwick. Beginning to question their loyalty and trust, Daryl kills Felicia by causing the girls to unknowingly cast a spell against her. Later that night, as Felicia rants to her husband about Daryl being the Devil, she begins vomiting cherry stones. Horrified by his wife’s sickness, Clyde beats Felicia with a fire poker, killing her instantly.
Terrified of the dangerous effects they had on the citizens of Eastwick, the three women agree never to see or speak to each other and Daryl for a long period of time. Fueled with anger and animosity, Daryl practices his powers against the girls by bringing their worst fears to life. Alex awakens into a bed of snakes, Jane transforms into an old hag, and Sukie is forced to feel intense and wrenching pain. Realizing the only way to rid Daryl from their lives is by using witchcraft against him, the girls reunite only to seduce and ultimately kill Daryl. The next morning, as Daryl visits town for a while, the women decide to practice a banishing spell against Daryl. As Sukie rushes to Daryl's office and takes a spell book titled "Maleficio", Jane gathers some personal belongings of Daryl, such as clothing, hair, and pictures, while Alex creates a voodoo doll out of wax, made to resemble Daryl. Once the spell begins taking effect, Daryl races home to punish the girls for their betrayal. Terrified of Daryl’s capability and power, the witches toss the poppet into the flames of a fire, causing Daryl to vanish.
Eighteen months later, Alexandra, Jane, and Sukie have each borne a son. Although they still possess their magical abilities, in fear of resurrecting Daryl, they choose not to practice them. As the women live together in the Lenox Mansion, Daryl attempts to communicate with his sons by appearing on television screens. However, worried of Daryl's diabolical intentions, the women avoid him by clicking the TV off.