Cartman is abducted by aliens and has a satellite going in and out of his anus to prove it. Meanwhile, Kyle has alien problems of his own when his brother Ike is also abducted.
Kathie Lee Gifford comes to South Park to present an award to Cartman. Cartman uses Weight Gain 4000 in the hopes of bulking up for the occasion, while Mr. Garrison makes some preparations of his own for Kathie Lee.
While on a hunting trip with Stan's Uncle Jimbo and his war buddy Ned, the boys learn about a monster named "Skuzzle-butt." Meanwhile, a nearby volcano is giving off signs of eruption.
The boys learn Stan's dog Sparky is gay. After several attempts to fix Sparky's "problem" fail, Sparky runs away. Stan decides to look for Sparky instead of quarterbacking the South Park Cows in the biggest game of the season.
When the boys learn about genetic engineering, Kyle wonders if it would be possible to cross-breed his elephant with Cartman’s pot-bellied pig. The boys enter their experiment in the science fair but have to compete against the son of Dr. Mephisto, the town’s genetic engineer.
Stan's grandfather is 102 years old and is begging for someone to kill him. When the boys are accused of attempting to aid Stan's grandpa in his wishes, the blame is put on Terrance & Phillip.
When mistakes are made at the morgue, Kenny turns into a zombie. Meanwhile, the town celebrates Halloween with costumes ranging from Chewbacca to Hitler.
While watching TV, a commercial featuring Sally Struthers comes on offering a free sport's watch with a donation to famine relief. Instead of a watch, the boys receive an Ethiopian boy, who they start calling "Starvin’ Marvin." When the government learns of the mistake, Cartman is mistakenly sent back to Africa instead of Marvin. Meanwhile, an experiment gone wrong results in mutant turkeys running rampant throughout the town.
While practicing for the Christmas play, the boys realize that Kyle doesn't celebrate Christmas. Kyle informs the boys that he does celebrate the annual visit of “Mr. Hankey, the Christmas Poo." Meanwhile, the town of South Park prepares to celebrate a non-offensive, non-denominational Christmas.
Damien, the son of Satan, is the new kid in South Park. Damien is in town demanding to speak with Jesus on his father’s behalf, which leads to an apocalyptic boxing match between Jesus and Satan. Meanwhile, Cartman prepares for his birthday party.
Mr. Garrison takes some time off for a surgical procedure and is replaced by a beautiful substitute teacher named Ms. Ellen. Wendy becomes jealous when Stan seems to be infatuated with Ms. Ellen. When Ms. Ellen seems to be immune to the charms of Chef, he tells the boys that he thinks she is a lesbian. After Mr. Garrison recovers from his surgery, he looks like David Hasselhoff and quits his teaching job to enjoy all that his new looks provide.
At an archaeological dig, Kyle picks up a triangle that Cartman has discarded. Media attention from the find attracts Barbra Streisand, who needs the triangle to complete “The Diamond of Pantios.” When she completes the diamond, she turns into a terrible monster that will require the combined efforts of Leonard Maltin, Sidney Poitier and The Cure’s Robert Smith to defeat her.
Cartman wants to find out who his father is, but his mom will not give him any answers. Learning that his father could be one of the many people that his mom "had relations" with during an annual party called "The Drunken Barn Dance," he enlists the help of Dr. Mephisto to uncover the truth.