Billy's pet hamster, Mr. Snuggles, celebrates his 10th birthday, so the Grim Reaper comes for him. However, Mandy, Billy's friend, is reluctant in allowing it, so she proposes a deal to the Grim Reaper: if he beats the kids in a game, he can take the hamster, but if he loses, he will spare the hamster's life and become their "best friend forever". The Grim Reaper transports the kids to limbo, where he challenges them to a game of limbo. Despite his best effort, Grim ends up losing because he is attacked by Mr. Snuggles at Mandy's own command. Hector Con Carne orders his staff mad scientist, Major Doctor Ghastly, to build him a new body after Boskov the Bear messes up Con Carne's latest plan for world domination by heading for food instead of battle. Billy's mother, Gladys, first notices Grim in Billy's bed, then in the shower and subsequently starts to get panic surges thinking that Billy is in danger. Meanwhile, Harold, Billy's dad, just thinks that Gladys is imagining things.
Billy and Mandy tell Grim it is "Opposite Day" and that, when they say something, they really mean the opposite. Due to his difficulty understanding the concept of Opposite Day, Grim has to do Mandy's chores. Finally, Grim thinks he understands when Billy and Mandy say they "want" pie, meaning they "do not want" pie. However, Mandy then says that when she said it was Opposite Day, it really was not. Major Doctor Ghastly makes her latest world-domination device, but General Skarr, Con Carne's Chief of Staff, uses the giant robot dog (modeled after Con Carne's tiny little chihuahua, Enrique Jr.) to attempt to kill Boskov and Con Carne instead of trying to take over the world with it. Grim is bored of being left alone while Billy and Mandy are not with him. Grim decides to fulfill his dream by working as a swimsuit model, but, as he is a corpse, he is not hired. Subsequently, Billy and Mandy give him a makeover to look more human.
Grim misses his life as the reaper of souls and, due to his bet, he cannot return to the Underworld, much to the hilarity of his Underworld co-workers. Having a sudden epiphany, Grim decides to be good and help people rather than try to take their souls. However, Grim's attempts at being good are faced with resistance from people, who are scared off by his appearance. Boskov is captured by park rangers and put in the zoo, where (true to form) Con Carne mobilizes the other captive bears to take over the world. After watching a movie, Grim teaches Billy to possess people by jumping into their heads. Billy possesses Mandy and makes her do assorted things like flirting with Irwin, kissing Mandy's mother, going into both men's and women's restrooms and eating earthworms. In the end, Billy leaves Mandy's head, but later that night, Mandy possesses Billy's cat, Milkshakes, to maul him as a form of revenge.
Major Doctor Ghastly's latest version of a world-domination device is The Almighty Stink Ray, with which Con Carne threatens to stink up the entire world unless he is given a huge ransom and small piece of land in Montana. Cod Commando, the only soldier without a nose, is sent to destroy the Almighty Stink Ray. Billy wanders into a junkyard, where a massive hole in the earth opens up and pulls him down in. Later, Mandy and Grim get pulled in as well. They land at the center of the Earth, which is home of Nergal, a devilish creature. The lonely Nergal, who has been watching Billy and Mandy for some time, wants Grim to hand over the kids to him so they can be his friends forever. Grim happily leaves the kids behind as he returns to the surface; however, he later goes back for them because he can't handle the guilt of abandoning his friends. In the end, Grim is defeated by Nergal's electrified tentacles, but Mandy defeats Nergal merely by kicking him in the shin.
General Skarr accidentally walks through Major Doctor Ghastly's devolving ray and begins to revert to his primitive forms, including a giant ape and starts to terrorize the Con Carne base. Billy, Mandy, Grim and Pud'n are part of the "Person Scouts" (a Boy Scouts-esque organization) and need to sell cookies in order to win a badge. However, as Billy eats all of the cookies, Grim proposes to bake their own cookies using his aunt Kali's secret recipe. The cookies are a success and the troupe wins the contest. In the end, at the Person Scouts awards ceremony, aunt Kali reveals that the secret recipe contains insects, but everyone continues eating the cookies anyway. General Skarr accidentally walks through Major Doctor Ghastly's devolving ray and begins to revert to his primitive forms, including a giant ape and starts to terrorize the Con Carne base.
Boskov goes into hibernation on the very day Con Carne has set for the invasion of the world. Con Carne gets away from the hibernating Boskov by breaking the container that houses him on the bear's head, then finds himself stuck in a pickle jar for the next six months, waiting for Boskov to come out of his winter sleep. While Spring cleaning in the middle of November, Billy takes an old, cursed lamp from Grim's trunk. When he gives it a rub, he releases the curse Grim had warned them about: his own mother. Having three wishes to make, Billy wastes his wish by wishing to know what to wish for. Mandy wishes Billy and Grim would "shut up", which causes both of them to zip their lips, so Grim never gets to make his wish. Then, Mandy decides to make the last wish to whoever makes her the happiest. In the end, Mandy wishes everyone in the world would go away, causing them, except Mandy, to disappear, which she is glad about.
After having a nervous breakdown and leaving the house in the first episode, Billy's mother, Gladys, returns. She meets Grim again and, this time, she plans to destroy him once and for all. When Grim goes to the kitchen for a glass of water, Gladys attacks him and shatters his skeleton. In the end, Grim assures the kids that Gladys has won the battle but not the war. Dr. Ghastly discovers that Hector's face may still be intact and sends out a search party to get it. This episode also reveals how Dr. Ghastly and Hector met, as well as how Hector was defeated by Cod Commando in the first place. With Irwin not answering the phone, Billy's parents missing and Mandy saying she wants "Billy for dinner", Billy and Grim assume Mandy is a cannibal who ate Billy's parents and friends. Looking for proof, Billy and Grim find tiki figures and arrangements for a celebration in Mandy's backyard. Ultimately, it is revealed that they are just celebrating Billy's birthday.
It's Halloween, Billy, Mandy and Grim go trick-or-treating. Grim mistakes a woman for Atrocia, the host of the all-night Halloween marathon on TV and goes to talk to her. Upon looking at her face, Grim realizes his mistake; however, the woman mistakes Grim for her son, Gregory, and takes him home Gregory is now Grim, and does not have a stomach. At the same time, Billy mistakes Gregory for Grim and he and Mandy take him with them. In the end, Billy and Mandy take Gregory back to his mother and Grim goes back with them. Skarr is evesdropping on Hector and Dr. Ghastly about their new secret weapon—a disenigration gun. Too their dismay Estroy comes up with a better version of the gun. He also surprises them by inviting them to dinner. Hector accepts as a way to steal some of his ideas. Hector and Ghastly arrive at Estroy's neighboring island while Skarr slips around the back. Of course he falls while scaling the wall and lands in a pond of electric eels.
Billy tells Grim to help him throw a surprise birthday party for Mandy. Then, a reluctant Grim helps Billy prepare a cake while keeping it a secret from Mandy. In the end, a somewhat surprised Mandy reveals that her birthday isn't here for the next five months, something that Billy already knew about. Con Carne takes over a Mister Rogers-type children's show in an attempt to rule the world by first winning over the children. Billy and Irwin have been playing their favorite video game, Beasts and Barbarians, for three days non-stop. In an attempt to stop their video game addiction, Grim transports them all to a real-life version of the game. Seeing as Billy and Irwin are still doing good in their quest, Grim increases the difficulty by manipulating the traps himself. In the end, Billy, Mandy, and Grim return home escaping from a giant cyclops, while Irwin remains trapped.
Billy, Mandy, and Grim go to the museum on a school trip. There, they meet Hoss Delgado, self-appointed hunter of the paranormal, who upon spotting Grim, tries to eliminate him. Subsequently, Grim and Delgado engage in a fight. Finally, Delgado quits hunting Grim when he realizes Billy and Mandy control him. In the end, Delgado continues his own adventures and is seen fighting a werewolf. General Skarr turns Con Carne in to the FBI when he finds out that Con Carne is "the World's 23rd Most Wanted" criminal with a large cash bounty on his head. When it turns out no lawyer on earth will defend Con Carne, he finds himself in court defended by Major Doctor Ghastly – and prosecuted by the Cod Commando. While going to the shopping mall with Billy and Mandy, Grim spots the beautiful Eris, the goddess of discord and chaos, and tries to ask her out. However, Eris is not interested in the skinless Grim, but in the muscular Adonis.
Billy eats too much junk food that makes him feel sick. Grim prepares him a remedy using his granny's recipe, but this medicine makes a parasite to start growing in Billy's back, which Billy names Yap-yap. In the following, Billy and Yap-yap continue eating junk food, so Mandy suggest to use the antidote to the original remedy. Eventually, Yap-yap, now looking like a smaller version of Billy, detaches himself from Billy (which would have technically cured Billy without the need of him drinking the anitdote), and tries to escape from the antidote. In the end, Yap-yap drinks the antidote and is destroyed. Major Doctor Ghastly invents the Temporal Confabulationater Izationizer Unit – a time machine that works so well that Ghastly, Hector and Skarr end up meeting their future selves and Destructicus Con Carne, son of Ghastly and Hector, as both an infant and an adult. Billy is constantly provoked by a bully named Sperg and runs over to Grim for help.
After taking the Underworld's "Bad Book" from Grim, Billy becomes possessed by an evil presence. Then, Billy steals Grim's scythe, and uses it to open a portal to summon Yog-Sothoth. In consequence, Mandy calls for Hoss Delgado to battle Billy. It is revealed that the portal can only be sealed by throwing the book into it. As Billy eats the book, Mandy throws Billy himself into the portal, restoring everything to normal. Instants later, a portal opens up and Billy comes out and says they didn't want him there. Rupert the Green-Nosed Reindeer saves Christmas when Hector Con Carne tries to ruin it. Mandy and her parents leave the city for a day, which makes Billy feel lonely. Then, Grim uses his supernatural powers to create a fake Mandy with pieces of dolls and toys for Billy to play with. However, the "new" Mandy is too aggressive with Billy, and he starts fearing her. The next day, the real Mandy returns home, and promptly destroys the new Mandy while in the see-saw.
In this musical episode, which pays homage to Little Shop of Horrors, Billy befriends a singing brain-eating meteor (voiced by Voltaire) that falls from the sky after when everyone doesn't want to play with him because they are busy. With Billy's help, the creature grows bigger and eventually eats the brains of all people in Endsville (turning them into zombies with glowing green eyes). The last brain he eats is Mandy's, which results in the creature transforming into a pink, brain-eating Mandy meteor. This is a mini musical. At first, Hector is singing about some of the things he adores. This leads into why he should take over the world (classical). This goes into Dr. Ghastly singing about her scientific work, leading into her baking pies for science (rock opera). The pies are sent to all the people who are singing about the temptation of pies in the sky. Skarr breaks in with a solo about hitting people with pies.