The novel begins with the narrator and protagonist, Mary Katherine “Merricat” Blackwood introducing herself. Merricat says that all of her family is dead except for her sister, Constance. She recounts a day of doing her weekly errands, such as going to the library and picking up groceries. These errands are difficult for Merricat because she’s afraid of her town’s hostile villagers, who she claims have always hated her family. She explains that her house is set apart from the town, closed off by a fence, and her family doesn’t even accept mail or phone calls. It’s clear that the hatred between Merricat and the villagers is mutual, since she often wishes them dead.
On her way home, Merricat goes into a cafe defiantly, trying to demonstrate her lack of fear towards the villagers. Two neighbors, Jim Donnell and Joe Dunham, taunt and pester her, the former claiming that he’s heard that Merricat and her sister are moving away (which proves to be false.) Eventually, the cafe’s owner, Stella, tells Merricat to go home. On her way home, a group of boys (the Harrises) sing a made-up rhyme about her sister Constance trying to poison her.
Merricat returns home to her sister Constance. In contrast to Merricat, Constance is sunny and cheerful. Constance begins to make lunch, and Uncle Julian, the third member of the sisters’ household, looks over his papers. These papers are dedicated to an incident six years earlier that killed the rest of the family. The sisters begin to prepare for tea with a neighbor, Helen Clarke, which is one of Constance’s few interactions with the outside world. When Helen Clarke arrives, the sisters realize that she has brought her friend Mrs. Wright. Helen Clarke, who Merricat clearly dislikes, urges the polite, kind Constance to go out in the world more often, reminding her that it’s been years since the family tragedy. Constance seems to be considering this idea, which she also joked about earlier, and this possibility alarms Merricat. In response, she smashes a pitcher in the kitchen.
Uncle Julian joins the women and begins to discuss the family tragedy: six years ago, the rest of the Blackwood family (the parents, the sisters’ younger brother Thomas, and Uncle Julian’s wife) were poisoned with arsenic at the dinner table. Uncle Julian himself barely survived the poisoning and has both mental and physical challenges as a result—for example, he uses a wheelchair and is easily confused. Helen Clarke disapproves of the discussion of the events, urging Constance to put them behind her, but Mrs. Wright is clearly curious. Uncle Julian reveals that Constance was tried for the murders of her family but acquitted.
Merricat wakes up the next morning anticipating change in her life, which she dreads. As a superstition, she chooses three magic words to prevent it. Dr. Levy comes to examine Uncle Julian later in the day. He again discusses the poisoning and reveals that he and his wife were afraid that the sisters’ father resented them as a financial burden.
The next day, Merricat wanders throughout her yard with her cat, Jonas. She reveals that she’s buried various objects of small value, including money, throughout the yard as a form of magical protection, and is startled to find that a book she nailed to a tree has fallen down, taking this as a bad omen. Later in the day, she sees a man coming up the stairs to the house and hides. Surprisingly, the agoraphobic Constance lets him in the house and explains that he’s their cousin, Charles Blackwood. Merricat is extremely upset by the intrusion of Charles and spends the night in a hiding place by the river with Jonas.
Merricat returns to the house the next day, convinced that Charles was a ghost. He comes downstairs, however, having spent the night in Merricat’s parents’ bedroom. Though he tries to be nice to Merricat, she refuses to speak to him. Uncle Julian, meanwhile, is excited to hear Charles’s perspective on the trial and the poisoning, but Charles doesn’t want to talk about it. Merricat and Constance clean the house according to their weekly routine. Charles talks to Jonas the cat in an attempt to get closer to Merricat, but she can only think of how to get rid of him. At dinner that night, Charles volunteers to go into town to get the groceries—Merricat’s usual job—and Constance is grateful.
The next day, while Charles is away, Merricat nails her father’s gold watch chain to a tree in place of the book. Charles finds it and is outraged that she would be so careless with something so valuable, and privately threatens Merricat.
Constance continues to doubt whether she should remain isolated as she has for the last six years. Merricat tries simply asking Charles to leave, but when he refuses, she smashes the mirror in his room. Uncle Julian also grows more wary of Charles. While Charles tries to fix a step outside, Merricat decides to magically cleanse the house of him and his influence. She breaks her father’s watch and fills his room with sticks and dirt. Charles, meanwhile, finds the money she’s buried, which further irritates him, and is furious when he sees what she’s done to his room. He wants to punish her, and is also angry at Uncle Julian, who, the novel reveals, believes Merricat in fact died at the orphanage where she stayed during the trial. Merricat runs away to the family’s abandoned summer house, fantasizing about the family showering her with praise and insisting that she never be punished.
Merricat returns to the house at dinnertime. She goes upstairs and tips Charles’s pipe into the trash can, which starts a fire. Charles soon smells smoke and discovers the fire. While Charles runs to find help, Uncle Julian tries to preserve his papers. Constance and Merricat hide on the porch while firefighters arrive. A crowd of villagers also gathers, and most of them are excited to see the house burn down, showing no concern for the Blackwood family. Charles is determined to get the house’s safe out, showing his concern for money above all, but it’s too heavy. Jim Donnell, the fire chief (who had taunted Merricat in the cafe at the start of the book) throws a rock into one of the windows after the fire is out, prompting the rest of the villagers to begin destroying the house.
As Merricat and Constance try to escape to the woods, the villagers surround them, laughing and taunting them. They finally disperse when Dr. Levy and Jim Clarke announced that Uncle Julian has died. The sisters show little reaction to this news, but flee to Merricat’s hiding spot by the river. Merricat says she wishes the villagers would all die like her family did before, prompting Constance to acknowledge for the first time that Merricat poisoned the family.
The next morning, the sisters discover that only the first floor of their house has survived. The house is covered with broken glass, dishes, furniture, and other debris, but Constance nonetheless makes breakfast. The sisters explore the rest of the house and find that the drawing room and dining room are both in a disastrous state. Merricat closes the doors to these rooms and the sisters never enter them again. Instead, they tidy up the kitchen and the hall and lock the door. Soon, the Clarkes appear at the door and insist that they want to help the sisters. Merricat and Constance hide until they leave, then cover the windows with cardboard to further isolate themselves. Later, Jim Clarke comes back with Dr. Levy and calls out that he wants to make sure that they aren’t hurt, but again, the sisters don’t respond. Constance apologizes for acknowledging that Merricat killed their family, promising that she’ll never bring it up again. Merricat describes the new pattern of life for the sisters. She constantly checks that the front door is locked and barricades the side of the house to further isolate the sisters. People begin to use the path through the front yard, and children sometimes play outside. Merricat never returns to her riverside hiding spot, deeming it too far from the house. Constance wears Uncle Julian’s old clothes, but Merricat, who insists she isn’t allowed to touch his things even though he’s dead, wears tablecloths.
Over time, the villagers begin leaving meals for the sisters on the front step with notes apologizing for the things they destroyed on the night of the fire. Charles returns once, begging Constance to let him in, but she refuses. Rather than being afraid, the sisters are amused, laughing hysterically once he leaves. Similarly, even as rumors spread that the sisters eat children and kids fear the house, Merricat and Constance delight in their isolation, beginning to laugh at the villagers rather than fear them. They consider themselves happy in their new lives.