The Simpson family is on a plate, as part of candies distributed on Halloween at a house. Bart is afraid of being taken, Marge conforts him saying he's always the last taken, and Homer saying even a box of stale raisins gets taken before him. Nelson's Crunch and Kirkish Taffy get taken, and Apple Lisa complains about no one ever wanting the apples, as people are afraid of razor blades being inside it. Marge conforts her saying they take them only when dipped in caramel, to Lisa's disgust. Shauna takes Senior Mints, after Homer moved aside, and eats its content.

The next day, the family is the only ones left, and they get placed on a shelf when the family remove the Halloween decorations, where they find a chocolate Easter bunny, that tells them they'll be left there forgotten. Seeing his disconfort as no one ever takes him, Homer starts eating him. Marge tries to stop him, but he tells her chocolate doesn't feel anything, and resumes eating it, with the rest of the family joining in when he eats the bunny's mouth to shut it up. The camera pans to the wall, where The Simpsons Easter Special is written, but the chocolate from the bunny splatters all over it, covering the words, and dark chocolate spells out Treehouse of Horror XXVIII.

In a pre-Christian temple site in northern Iraq, a Pazuzu statue is dug up and sent through Amazon to the Simpson home after Homer ordered it, thinking it was pizza. After Homer, who is possessed, sings the Pazuzu Lullaby to Maggie, the statue is placed across from Maggie on her crib, and right after Homer leaves, Pazuzu promptly possesses Maggie.

Meanwhile, Marge and Homer are having their cocktail party downstairs, but Marge notices the possessed Maggie making her presence known. She proceeds to kill a complaining Helen Lovejoy before locking everyone indoors, and then killing Dr. Hibbert after revealing that he is cheating on his wife with his nurse. Later, Ned Flanders tells the Simpsons that Maggie needs an exorcism, but he is killed while trying to hold her down.

Homer and Marge succeed in tying the possessed Maggie down with bible ribbons and she starts to turn her head 360 degrees. Eventually, an Irish Catholic priest arrives, and, after testing how powerful Pazuzu truly is, performs the exorcism that purges the demon from Maggie, but Pazuzu ends up possessing Bart, which he fearfully regrets, declaring that Bart has the evilest soul he has ever seen.

Bart tells Pazuzu to grow him some horns, which Pazuzu does. Homer notices the horns are nubs. Pazuzu then grows the horns so long that they impale through Homer's nose. Uncomfortable, Homer says that at least the horns will get him out of jury duty, but later, Homer is later seen sitting on a jury with a dismembered horn still through his nose, to which he shouts, "D'oh!"

Maggie has still got a touch of Pazuzu while starting to violently vomit all over the dinner table. In Lisa's room, Snowball V takes her through a secret tunnel that brings her to another version of the family, with buttons instead of eyes on their faces. While the alternate family are like a dream, Lisa runs back to her world in terror when she learns they want to sew buttons on her eyes so she can remain with them forever. Lisa reconsiders the alternate family's offer after Homer had killed a snake using Lisa's saxophone.

A few days later, the family finally realizes that Lisa is missing, with Homer accepting it and saying that Maggie gets Lisa's room and clothes, while Bart gets her homework. Upon hearing this, Bart escapes through the door and is accepted into the alternate reality. Marge follows the kids and Homer follows suit. A meeting with the alternate family results in his killing alternate Bart while alternate Homer injures himself on a pair of scissors trying to avenge him. This irritates alternate Marge who transforms into a spider-like creature to attack Homer, who chooses to take advantage of the situation to benefit himself: bringing the surviving members of the alternate family home with his alternate counterpart attending parent-teacher meetings while alternate Marge does the chores and guards the house. Lisa accepts this outcome, noting that it could have been much worse.

Lisa warns viewers about the following segment s disgusting content, proclaiming that they may want to watch Game of Thrones afterwards to calm down. The segment, then begins with Homer being the only one left home, while the rest of the family go on vacation with Patty and Selma. Homer gets comfy, but ends up eating all of his food supplies, leaving him with vegetables left to eat. He finds a frozon hot dog, but loses it to Santa's Little Helper.

Homer accidentally cuts his finger off while grilling. Since his severed digit got cooked, he decides to eats it. after discovering how tasty it was, he loses interest in other food and starts cooking parts of his body before his family come back. They become suspicious with Homer constantly wearing oven mitts to hide his severed fingers, being 20 pounds thinner, and walking with a limp. When Marge discovered Homer's self-cannibalism one night while he was frying his own severed leg, she took him to an addiction counselor for help.

However, Mario Batali, in search for new ingredients, convinces a despondent (and now missing the entire lower half of his body) Homer to cook his remaining body parts as ingredients sold at Chez Homer and several other restaurants across Springfield. Carl mentions that they are also eating Barney Gumble, Comic Book Guy, and horse meat.

In Heaven, Homer comments to Jesus how he now shares people eating his body with him, as the Springfield residents have turned into cannibals.