It is Halloween night in a Dr. Seussian take on Springfield. The Simpson children are home with the mumps and unable to go trick-or-treating. Once their mother Marge (in a Catwoman costume that every other woman and The Comic Book Guy is wearing) leaves for a costume party, they are visited by The Fat in the Hat (Homer) who gives them vaccinations so he can take them out to get candy for them and beer for him. However, instead of helping the children get their treats, he takes them on a path of death and destruction; blowing up Mr. Burns' mansion and feeding him to a homeless shelter, robbing Moe and skinning him, robbing Apu and forcing him to spend time with his wife and children, killing two DMV workers (Patty and Selma) and tossing car licenses to people waiting in line, blowing up town hall while wearing a Guy Fawkes mask, and committing "aggravated Flu-Fluffel-cide."
The children are alarmed at those events and manage to elude him with the aid of several animals; a Barney Gumble-esque camel, a Krusty-esque bull, and on the wings of the Mexican Bumblebee Man. However, Fat is waiting for them when they get home and gloats that he will never leave them right before baby Maggie stabs Fat in the chest with his own umbrella. Marge comes home, unaware of what happened, and the children fake their mumps by stuffing the collected candy in their mouths and have turned the Fat in the Hat into a rug.