In the opening scene, Kang and Kodos (without their helmets) introduce the show, with a live audience consisting of aliens. While they tell jokes, canned laughter is played, but the audience appear unamused.

The Simpson family sits on the couch, with Homer appearing as the jack-in-the-box from "Treehouse of Horror II", Marge as the witch from "Treehouse of Horror VIII", Bart as the half-fly mutant from "Treehouse of Horror VIII". Maggie is the alien/human mutant from "Treehouse of Horror IX" and Lisa is the victim of an ax murder. Lisa then asks what aliens have to do with Halloween, and Maggie, in a deep voice, says, "Silence!", and disintegrates her with a ray gun.

The Simpsons are driving when Marge runs over Ned Flanders, killing him. The next day, Homer stages Ned's death. Soon after Ned's funeral, during which Homer almost unwittingly confesses to Ned's murder, the family finds the words "I Know What You Did" written on their house and car. They are terrorized by a cloaked, hook-wielding figure, and flee. When their car breaks down, they discover that Ned is the cloaked figure. He was not killed because he was bitten by a werewolf just before the accident. The full moon appears and Ned turns into a werewolf. Marge, Bart, Maggie and Lisa run away but Homer is caught, and taunts the werewolf while he is mauled to death.

A malfunctioning X-ray machine gives the ability to stretch any part of his body to Bart and super strength to Lisa. They become a superhero duo, calling themselves "Stretch Dude and Clobber Girl". Lucy Lawless addresses fans at a science fiction convention. Comic Book Guy, now a villain called "The Collector", kidnaps her and takes her to his lair with the intention of marrying her. Stretch Dude and Clobber Girl arrive to rescue Lawless, but are also captured. The Collector prepares to kill them by submerging them in a vat of molten Lucite. Lawless pretends to be attracted to the Collector and then clobbers him. The Collector grabs his limited edition double edged lightsaber from Star Wars: Episode I The Phantom Menace and ignites the blades, but when Lawless points out that he has removed it from its original packaging, he panics and falls into the Lucite. Lawless flies the children home.

On December 31, 1999, Homer, the Springfield Nuclear Power Plant's Y2K compliance officer, has neglected to fix all possible problems in the plant's computers. This results in a computer virus causing widespread destruction and societal collapse. The family learns that a rocket is being prepared for humanity's "best and brightest", and will carry them to Mars to preserve human civilization. Homer fails to bluff his way on board but the guard recognizes Lisa as the ship's designated proofreader. Lisa is only able to take one parent with her, and chooses Marge. Homer and Bart find a second, unguarded rocket. They quickly notice that it is filled with second-rate celebrities. While this rocket is headed directly for the sun, Homer and Bart cannot bear being with these passengers and eject themselves into space.