Scarlett Winslow and her house-flipping fathers Michael and Troy move into the infamous Murder House. Scarlett sneaks out to attend a sleepover at her crush Maya's house. Later that night, Maya invites Scarlett back to her bedroom away from the others. They kiss and Scarlett shares her violent sexual desires. Texts from her best friend Shanti reveal to Scarlett that Maya and her friends are pulling a cruel prank on her by live-streaming their conversation. To get revenge after a fantasy of one while masturbating, Scarlett lures Maya and her friends to the basement of Murder House, where she murders them, while wearing the Rubber Man suit. The next day, Scarlett opens her door to find the Rubber Man outside.

Scarlett forms a relationship with Ruby, the ghost of a young woman who snuck into the Murder House to commit suicide as they relax in the same bathtub. Troy begins to cheat on Michael with a contractor named Adam. After discovering the bodies of Maya and her friends behind a brick wall, Adam blackmails Michael and Troy only to be slain by the Rubber Man. Michael and Troy try to flee the house, but find they cannot leave. They find out that they were murdered earlier in an effort on Ruby's behalf to persuade Scarlett to stay with her in the Murder House forever. On Halloween, Scarlett and Ruby venture out of the house. The ghosts of Maya and her friends pursue them to get revenge on Scarlett, but they are unsuccessful. At dawn, Scarlett resolves to move out of the Murder House while promising Ruby that she will visit her every Halloween.

Kelley and her boyfriend Chad attend a drive-in screening of a banned film "Rabbit Rabbit". The film was banned thanks to Tipper Gore after it caused the premiere's audience to kill each other upon their eyes turning black. The film's director Larry Bitterman attacks Tipper at a congressional hearing after she gloats about the studio burning all remaining copies. He is subsequently jailed for the assault. In the present, Kelley and Chad make out as the film starts. Unable to see "Rabbit Rabbit" through fogged-up windows, they are unaffected as mass violence erupts. Everyone who watches the film is attacking and devouring one another. Kelley and Chad flee to the projection room and destroy the film. Hours pass and instead of going to the cops, the two decide to find Larry and force him to hand over all copies. Once found, Kelley shoots Larry's kneecaps and Chad burns the original film. Larry taunts them as his trailer burns down and they leave him for dead. The two go back to Chad's and celebrate. As they kiss, the camera pans to "Rabbit Rabbit" being promoted on Netflix. Then the window shows the Los Angeles skyline erupting in flames.

Influencers Wyatt, Zinn, Barry, and James live in a content house and have a collaborative YouTube channel, "The Bro House". Their channel begins losing subscribers after they post a video of a man jumping off a bridge. After failing to regain their popularity by queer baiting, the boys film a prank video at a mall's Santa Village where they make fun of a Mall Santa. On Christmas Eve, the boys upload the video and they get a call from a detective stating that the Santa in their video was an imposter as the real Mall Santa was found dead. The imposter Santa descends upon their house, killing Wyatt and Zinn and uploading their deaths onto the Bro House channel, along with a linked article identifying himself as the Wild Man, a minor pagan god and Satanic killer of the "naughty" after whom the legend of Santa Claus was inspired. Barry and James try to escape the house but the Wild Man shoots them down in the driveway. James is killed and Barry drags himself back into the house. Their channel reaches five million subscribers as the Wild Man pours gasoline down the chimney and sets the house and Barry on fire, who jumps into the pool to put himself out. On Christmas Day, the police find the other boys' body parts adorning their Christmas tree, as elsewhere, the Wild Man prepares to murder another Mall Santa.

After several failed attempts to get pregnant, Liv Whitley receives a totem from Bernadette, the receptionist at a fertility clinic, and places it under her bed just before she and her husband Matt have sex. The totem works and Liv has a son, Aaron. Sixteen months later, Liv is suffering from postpartum depression and begins seeing visions of Ba'al, a demon haunting her child. Liv seeks out Bernadette, who shares a banishment ritual with her. Liv accidentally stabs Matt while performing the ritual and is committed to an asylum. It is revealed that Matt and his college friends had orchestrated every supernatural event to gaslight Liv so Matt could have her committed and take her money to share with his friends; Matt had never wanted to have a baby, had been sabotaging their efforts to get pregnant on purpose, and had been having an affair with Bernadette the entire marriage. As Matt and his friends celebrates his success, the real Ba'al appears and slaughters Bernadette and Matt's friends. It is revealed that Liv sent Ba'al to exact revenge. The banishment ritual Bernadette gave her turned out to a "real life summoning spell". Matt is sent to prison and Ba'al appears in Liv's bedroom. He demands to be released; She agrees on the condition that "You give me another baby".

A boy named Jacob Gantz disappears on a camping trip with his parents Jay and Addy. Ten years later, a hunter named Bob offers to take them into the woods to find Jacob. Once there, the group is hunted by wild deformed humans. Bob reveals it was all a hoax and he plans to rob them. Bob is attacked and devoured by the wild humans. Jay and Addy seek refuge at a ranger station staffed by a park ranger named Stan. He divulges that the National Park Service was created by the government to protect the public from the "Feral Nation", a subpopulation of feral cannibals that have an indeterminate origin. As Stan tries to radio his superiors, the ranger station is attacked by the ferals and Stan is killed by a rafter feral. Jay and Addy flee and find that their now-grown son is now the leader of the ferals and sitting on a throne of bones. When a tall bearded feral asks Jacob who they are, he responds in their language "dinner". The ferals swarm over Jay and Addy to devour them as a blood splatter lands on Jacob's cheek which he wipes off with his finger and tastes.

Video game designer Michelle enters the Murder House on Halloween Night to conduct research for her newest game, based on the legend of the house. While there, she is stabbed to death by Ruby and Scarlett. One year later on Halloween, Michelle finds her son Rory and claims there is no escaping the Murder House. Rory offers to burn it down, but Michelle refuses. Ignoring his mother, Rory shows up with gasoline canisters. While Ruby tries to stop him, she in turn is stopped by the other ghosts who are tired of their suffering. As Scarlett arrives to help Ruby, the house is set ablaze. Three years later, condos have been built where the Murder House once stood and Scarlett purchases the last unit to reunite with Ruby who mentioned that the other ghosts have crossed over. It turns out that the events of the story have been a playthrough of the finished video game which Rory is impressed with.

Crazed dollmaker Van Wirt kidnaps Coby to bring her to his personal doll collection on his property. She joins several other kidnapped women: Aurelia, Harlene, Faye and Bonnie. They tell Coby that after murdering his adulterous wife, Van Wirt wants a replacement mother for his son Otis and has decided that the women should compete for the honor in a "pageant". Otis warms to Coby, who entertains him with her powers of telekinesis. During the pageant, Faye and Bonnie fail Van Wirt's tests and are killed. The remaining women plot to escape. Coby refuses to leave without going back for Otis, but is captured and Van Wirt's assistant Eustace kills Harlene and Aurelia. Since Coby risked her life to save Otis, Van Wirt declares her the winner and encases her in plastic to serve as a living "doll." However, two witches arrive and identify Coby as one of them. They rescue her and set fire to the house, killing Van Wirt and Eustace. Coby and Otis join the witches at Miss Robichaux's Academy. Now going by his middle name of Spalding for his own safety, and raised by Coby, Otis meets a girl named Myrtle Snow.

After moving home, Jaslyn buys Aura, a smart doorbell device. Aura's camera shows her an old man outside; he calls out to her by name and attempts to enter, but there is no trace of him. Jaslyn's husband Bryce believes it is a prank, but she realizes the man is the ghost of Mr. Hendricks, the janitor at her high school. Hendricks apologizes for sexually harassing her in the past, then disappears. Another ghost soon appears via Aura, and Bryce again insists it is a prank. Jaslyn learns that Aura detects spirits through electromagnetism and that the ghost Mary Jeane died in an apparent hit and run. Bryce confesses he was previously engaged to Mary Jeane, but pushed her in front of a car after learning she was pregnant; the car did not kill her, so he broke her neck. He attacks Jaslyn, but is killed by Mary Jeane's ghost. Three months later, Jaslyn has moved into a new apartment that has Aura installed. Bryce's enraged ghost appears on Aura's camera and attempts to break into the apartment.

At the end of a night out, Marci is chased by an unknown man in a Jeep. She is determined to continue partying in clubs, despite being warned by her husband Chaz about news reports of local people disappearing from clubs. Chaz feels that their open marriage is no longer working and decides to separate from her. Meanwhile, her friend Piper is critical of Marci's lifestyle. Marci traces the Jeep's owner Paul and she later follows him home. Paul says he chased her on the road to warn her that someone was in the back seat of her car. Marci reveals that she is a serial killer and goes to clubs to find victims, one of whom he saw in her car. She tortures and kills Paul as a witness to that murder. Chaz agrees to give their marriage another chance and to help Marci with the murders, which she believes will bring them closer together. Sometime later, Chaz and Marci kill Piper together.

In 18th-century New England, a village has been devastated by smallpox. Thomas Browne tells the village pastor Walter of rumors that smallpox can be cured by eating the hearts of recently deceased victims. Walter does so and encourages his congregation to follow suit. The local people shun the prostitute Celeste who had tried to warn them that Walter is corrupt. She takes refuge with a milkmaid named Delilah and the two begin a relationship. Delilah realizes that she and Celeste have previously contracted cowpox and this has given them immunity to smallpox. As the villagers eat hearts straight from the corpses of the dead, Delilah begs them to stop and offers them milk from an infected cow to protect them against the disease. Walter publicly denounces her. He assaults Celeste and stabs Thomas, who reveals that Celeste is the mother of his son Edward. Delilah kills Walter, but is also killed herself by Thomas before he dies from his injuries. Celeste reveals herself to Edward as his biological mother, only for Edward to repeat Walter's statement that a milkmaid is unclean (after Celeste casually identifies herself as one) and stabbing her in the stomach, before cutting out her heart to eat it.

Sisters Elise and Bianca hear from their friend Lena Lawrence about the legend of Bloody Mary who will grant the desires of those that swear loyalty to her. The girls each summon Mary, who instructs them to use unethical means (such as hurting someone) to get what they want. Lena and another friend named Maggie disobey Mary's orders and are subsequently found dead. Elise discovers that Mary was an escaped slave and was held at a cabin after being re-captured. With this information, Elise and Bianca devise a plan to summon Mary at the cabin and kill her. Mary appears and Elise reveals that Mary asked her for blood from three innocent people; she killed Lena and Maggie and now intends to kill Bianca. However, Bianca kills Elise in self-defense. Mary explains that her spirit became trapped after she misused the powers of the deity Mami Wata for revenge. Bianca fulfills her promise by offering her soul to Mary. This releases Mary and Bianca replaces her as the new "Bloody Mary" as she makes plans on what to do with anyone who plans to summon her.

Virginia Mallow, a woman in late middle age, wishes to look younger. Her acquaintance Cassie refers her to Dr. Enid Perle who carries out anti-aging procedures. While recovering, Virginia suffers excruciating pain and is tormented by visions of demons. She rejects her stepdaughter Fay who views Virginia as her real mother. Virginia is moved to Perle's private lodge to assist with recovery. Fay has become suspicious of Perle and follows Virginia to the lodge, but is caught and sedated by security. Virginia's bandages are removed and she sees that Perle has given her a disfigured porcine face. Perle and her staff are a cult that worships beauty and Virginia is to be their annual ritual sacrifice to the deity Étaín. Virginia is released onto the lodge grounds and attempts to escape, but is hunted down and killed by the cult members including Cassie. Perle tells a distraught Fay that her birth mother was one of Étaín's followers. Later, a more confident Fay returns to university with the cult's signature butterfly tattoo. She recognizes a young man as another member of the cult who asks about it. They walk together to their destination.

In 2022, Sam is a mortician in California, working under Henderson, who has trouble connecting with anyone due to finding her mother murdered when she was just a toddler back in 1998. While working, she meets Charlie who also works at the mortuary as a new body removal technician. They form a kinship over their shared beliefs about the dead. After sharing his own personal trauma, he tries to get Sam to open up about hers. A misguided attempt to do so involving Charlie posing as a corpse and Sam having sex with him leads her to reevaluate her life. However, video evidence of her actions follows her everywhere making her unable to find other employments and leads to a confrontation between Sam and Charlie in a graveyard where they acknowledge that they are the only ones who understand each other. Sam then shoots Charlie and joins him in a freshly dug grave, making out with Charlie's corpse as it is being filled back in.

Jake and his sister Finn dive into Lake Preston and explore its bottom where a hand drags Jake and drowns him. Four months later, Finn returns home after leaving a mental health facility. After their mother Erin gets startled from seeing Jake's hand emerging from the bathwater, she researches and dives into Lake Preston. Erin finds Jake's corpse and three skeletons chained to a concrete pillar and removes one's necklace. Erin and Finn meet Millie Boone who explains that the necklace is tied to the Boone family and that it belonged to her great-grandfather Maynard who was amongst the three opposing Wrede Prescott's development of the dam and that he was among those left to drown during the formation of Lake Preston. Jeffrey catches up to them and mentions he is part of the Prescott family. Erin realizes that the underwater attacks are retribution towards the Prescott family. A mob of zombies emerge from Lake Preston and drag Jeffrey in. Finn and Erin mourn him whilst conferring that the secrets about the dam's development will eventually be discovered.

Shelby moves to a new house and school after her mom dies due to cancer. She is quickly picked on by a group of kids due to her appearance and takes her anger out on her father. While watching her favorite YouTube show Anna Rexhia, another watcher named BFF4EVA contacts her wanting to videochat. It's revealed that the person is a deformed teenage girl who quickly befriends her and the two-bond due to their loss of mothers and annoyances of their dads. BFF4EVA/Bestie later encourages her to be more confident and do a series of escalating pranks like shoplifting, getting in fights with her dad, and poisoning the entire cast for a school play into vomiting on opening night. She finally goes overboard when she goes as her music teachers' stillborn baby on Halloween and is locked in the basement by her dad as punishment. Bestie calls her on an old laptop and tells her to break her arm to get out. This is the breaking point as it makes Shelby re-evaluate her relationship and stops being friends with bestie. She apologizes to her father and teacher and befriends a boy named River who bonds with her because he experienced bullying due to his disabilities. One day River takes her to a house that he believes to be haunted but while there, Shelby realizes it's Bestie's house after recognizing the scenery. Bestie appears and Shelby tries to flee but River stabs & kills her, revealing he is another one of Bestie's "friends". The two walk out towards the sea and hug.

In a world where a new pandemic causes everyone to be in lockdown, art curator owner Will Caswell is given a high-tech assistant named Daphne. As he is alone with only Daphne for company, he lets her in and she proceeds to make his life better: changing lights in his home, raising prices on virtual art auction, and helping him sleep. When lockdown is lifted due to a vaccine, she grows upset when he is intimate with his girlfriend Sarah. She first tries to sabotage their relationship by admitting that she faked an orgasm and then not making dinner reservations. Later she replaces her takeout with food cooked in peanut oil which results in her dying. At a physical art show, Will brings Daphne who ends up killing everyone at the show, except for him as he left the room. Upon returning home, he is arrested for Sarah's murder due to footage showing him changing out Sarah's food order and the murder of the art goers due to his tampering with the room. At the precinct, he learns that Daphne had been a gag gift and for others didn't work the way it did for him. He continuously tries to get Daphne to talk for the police while the device remains silent.

A peppy woman named Vivian attempts to audition for a role at Vogue but an agent named Sheila Klein tells her she's too fat to be a model. Her friend Heather gives her a card to a weight loss doctor named Dr. Thaddeus Lau who gives her medication called Mondify that causes her to lose weight and later on she gets a job at Vogue. However, during a photo shoot, she faints and breaks her nose. During a checkup with Dr. Lau, it turns out that she has a heart condition that could be fatal if she keeps taking the shots. He gives her another option which is a tapeworm that would eat anything she eats and never give her any weight, but she must not overeat. She does so anyways and later on as she continues to get more jobs, the worm begins to cause her to change in her eating behavior and personality causing her to yell at her coworkers and Heather. The worm causes her to lose so much weight that she becomes very skinny. After meeting with Lau, he gives her a serum that will cause the worm to exit through her anus and at home, she takes the serum and pulls the worm out. Unfortunately, the worm is still alive and then kills her. When Heather comes back to get her stuff, the worm attacks her and inserts itself into her through the mouth. Later Heather auditions for Vogue and gets in claiming that "she's starving", starting the cycle all over again.

A sexist, selfish womanizer named Toby is in trouble at work due to his obsession with woman but refusal of commitment. While searching for a new date, he finds a beautiful woman Natessa and they go out. When their about to have sex at his house, she injects him with a syringe and he wakes up the next morning finding a large bleeding stitch on his stomach revealing she was an organ harvester. After going to the doctors, he learns that in addition to losing an organ, he also got a mysterious unidentifiable organ that the doctors can't tell what it is. He then goes to his former hacker friend and blackmails him to gain info on Natessa. He finds her at an auction selling organs and he forces her with a gun to follow him outside and tell him everything. She reveals that she is actually an English actress and that a mysterious company paid her to just inject him while they sent a team of doctors to harvest his organ and replace with the new one. When she begs to be let go, he accidentally shots her and she dies. Toby tells his friend Sasha and tries to attempt to convince her to run away with him but she refuses and begs him to tell the truth to the cops. However when Toby takes the cops to the auction site, he finds everything and everyone gone and the cops arrest him. However on the drive to the station, he figures out that they are also part of the organ harvesters and he is taken to their company. Their leaders are revealed to be Sasha and his boss Lee and explain to the new organ in him is called a glans nattali. An artificial organ that can enhance the life of a person (specifically a woman) and that they plan to harvest these from dozens of people and subtly reveal that by taking it out will result in that person's death. After extracting Toby's nafftali off-screen, the two women watch from afar as it is sold off to another woman, who is revealed to be Toby’s psychologist.