The story, set in the fictional Rhode Island town of Eastwick in the early 1970s, follows the witches Alexandra Spofford, Jane Smart, and Sukie Rougemont, who acquire their powers after their respective marriages end.

The three women share Darryl in relative peace until he unexpectedly marries their young, innocent friend, Jenny, the Gabriels' daughter.

Although Alexandra feels remorse for their hex, the spell kills Jenny and Darryl flees town with her younger brother, Chris, apparently his lover.

[1] In 1987, the novel was adapted into a film starring Jack Nicholson as Darryl, Cher as Alexandra, Susan Sarandon as Jane, and Michelle Pfeiffer as Sukie – with considerable differences from the book's plot.

In 1992, a television series pilot aired that was directed by Rick Rosenthal and starred Michael Siberry as Darryl, Ally Walker as Alexandra, Julia Campbell as Jane, and Catherine Mary Stewart as Sukie.

In 2002, The Witches of Eastwick musical opened in Australia, starring Paul McDermott as Darryl Van Horne, Marina Prior as Jane Smart, Pippa Grandison as Sukie Rougemont and Angela Toohey as Alexandra Spofford.