When Billy's parents are attacked by an anaconda, Billy suggest visiting boy wizard Nigel Planter, because he can talk to snakes. Planter in fact does not speak to snakes, but to snacks, and instead he asks for Billy, Mandy and Grim's help to win the affections of Huffefnie Pfefferpfeffer, a beautiful witch in the School of Sorcery (and having a striking resemblance to Gladys). Planter tries using a romantic love potion and enchanted chocolates, but they do not work. The guys end up completely forgetting about Billy's parents.

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.

General Skarr buys a home in Endsville and becomes Billy's neighbor. After Skarr invites Billy into his new house, Billy mentions Grim's scythe as ,he strongest and most powerful weapon in the entire universe, and Skarr tries to battle his desire to be evil again. Eventually Skarr steals the scythe but Mandy proves to be even scarier than he is, and takes it back.

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. In the end, Grim gets the job in a TV ad, but he is only in the commercial for a few seconds and is portrayed as an ugly person.

When Billy decides he wants to grow up to be like Grim, he says nothing will stand in the way of their friendship. They meet a girl named Blandy, who looks very much like Billy, and Billy falls completely head-over-heels in love with her. When Blandy shows romantic interest in Grim, Billy is struck with mad jealousy and wants Grim out of the picture. Mandy consults Grim's encyclopaedia of monsters and realizes Blandy is actually a creature from another dimension. Despite Blandy showing her true form and leaving, Billy remains madly romantically infatuated with her; but only up until the following episode.

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.

At school, Billy, Mandy, and Irwin look for a club to join. Irwin plans to join the Macrame club to meet girls; Billy inquires on the Junior CIA club, which forcefully recruits him; Mandy joins the "Secret Snake Club", a snake-themed club consisting of three geeks. The nerds reveal that their "secret agenda" is to resurrect Shnissugah, a giant snake which lived hundreds of years ago in Canada, to take revenge against the popular kids, but they lack the power of the Underworld to do so. Mandy calls for Grim, who proceeds to revive Shnissugah through the internet. Billy, as a junior agent of the CIA, stops a criminal plan by Irwin, who was using the Macrame club for personal gain; and Shnissugah turns out to be a tiny, 8-cm (3.14-in) long, harmless snake.

When Billy finally gets a "secret decoder ring" in his Blasto Bits cereal, he receives a holographic message from a strange creature who speaks about finding the "Secret of the Universe" in an abandoned mine shaft. All the other children of Endsville, also with decoder rings, race to the mine to be the first one to get the Secret. The entire effort is revealed to be a trap laid by Lubbermouth, a worm-like creature from Grim's past, who wishes to free herself from the curse of guarding the Secret. When Mindy looks down at the pit, she becomes the new guardian of the Secret and has to stay there forever.

When Billy goes to visit his maternal grandmother and Mandy decides to have the day for herself, Grim finds himself free of the kids to do whatever he wants to do. Since Grim quickly gets bored he goes to visit General Skarr, and lets him take his magical scythe, which Skarr uses to build an army of giant lawn gnomes. Since Grim is so used to having two kids with him when they go on an adventure, he enlists Mindy and Pud'n to help him combat Skarr and retrieve his scythe. Mindy and Pud'n prove to be worthy substitutes but they are scared away by Mandy when she notices the unusual trio

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 command.

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. In the end, Gladys ends up going living with Billy's aunt, Sis to try and calm herself down.

As Billy desires to be "cool" like Sperg, he has an ectoplasmic manifestation coming out of his mouth. The ectoplasm grows full size and turns out to be the ghost of nineteenth-century British poet Lord Byron, who tries to teach Billy to be cool, using elaborate poetry instead of bare muscles. Billy uses a poem to insult Sperg's mother, and Sperg challenges Billy to a duel. Billy and Lord Byron fight Sperg and his gang, but are badly beaten. Byron tells Billy he has been trained in the arts of coolness, and disappears.

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.

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", 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, which she is glad about.

As Grim watches the entire season of "My Troubled Pony" (parodying My Little Pony), he learns from Mandy that the show was cancelled and does not have an ending. Grim decides to reap the "Schlubs" (a parody of The Smurfs), 100 creatures that live in Billy's yard, to melt them into gold so he can finance the creation of the series finale. Grim must get past Billy and the aggressive Schlubs themselves, including the single, large female (a parody of Smurfette). After Grim thinks he got the creatures with his scythe, Mandy appears to have used all the gold herself to become rich.

When Billy digs his front yard he finds a frozen caveman, who is actually Fred Flintstone (from The Flintstones), but whom Billy names Jake Steele. Billy tries to acclimate Fred to the modern life but the job is not easy. When Fred is taken to school, he predictably goes out of control, kidnapping Miss Butterbean and running away in Principal Goodvibes' car. The ensuing chase results in Fred crashing into an ice cream truck, becoming frozen again. Instead of reaping him, Billy decides to bury Fred in the yard again. A future is shown where both Billy and Fred are defrosted by brain-eating creatures.

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 for the next five months, something that Billy already knew about.

At a father-and-son picnic, Billy re-encounters with his spider "son", Jeff, in a dirty bathroom. Once again, Jeff tries to make Billy love him as a true father does, but Billy remains terrified of all bugs. Mandy tells Jeff he is being too nice, and to get Billy's attention he needs to be meaner. After being coached by Mandy, Jeff finally snaps and ensnares Billy in his spider web, forcing Billy to say he loves him.

When Nergal goes to visit Billy's family (his in-laws) for the weekend, he ends up staying with them over a year. When Billy finally asks his uncle to leave, Nergal says he cannot return home because he is a complete failure, having lost at a board game 599 times in a row against his own family, and experiencing constant disappointment elsewhere. Billy and Grim tell him to not worry about being a failure, but to embrace it. After training with Billy and Grim, Nergal returns home and he finally wins at the board game, but he also makes a crack in the ceiling and his home starts filling with lava.

When Billy's dad gets a promotion at his job, he tells his family they are going to move to another town, starting a dispute between Billy and Mandy over who gets custody of Grim. Grim suggests they settle this in court, and hours later Billy, Mandy and Grim find themselves in the Underworld court, presided by Judge Roy Spleen, and which has Fred Fredburger, an incorrigible dumb character, as a juror.

Billy, Mandy and Grim visit Mighty Moe, an old man who has discovered the secret to add extra years to his lifespan: a good diet and exercise. Mighty Moe decides to publish his secret in a book, and Grim needs to stop him by offering junk food.

When Billy and Irwin want to watch classic giant monsters movies, Grim decides to take them to Japan to see real monsters. They meet the turtle-like Cragorah (a parody of Gamera) who engages in a fierce battle with the three-headed Kittirah (a cat version of Ghidorah). To help Cragorah, Grim transforms Billy into a giant monster too (a parody of Ultraman). Mandy soon arrives with the intent of punishing them all for organizing this expedition without her permission. Controlling Mecha-Gorillasaur (a giant gorilla robot) she defeats Kittirah and beats Billy.

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.

When Billy and Mandy are utterly bored, Grim takes them to Underworld's "Circus of Fear". The ringleader, Dr. Fear, notices Billy and Mandy, and tries to recruit them into the circus to attract customers, who would pay to see real, live humans. After they go back home, Dr. Fear captures the two kids, and Grim has to get them back. During the show, Mandy breaks free and in a strange twist of the story, she reveals that the beastmaster, Clortho, is actually Dr. Fear, who in turn is just an earthworm, leaving Billy confused.

After a trip to the mall, Mandy becomes the spokesperson for Happy Huggy Stuffy Bears, a new stuffed toy in town. After the success of her commercial, Mandy gives away stuffed bears to other children, who start wreaking havoc in the city. Eris, the goddess of chaos, is behind the toys, which mind-control the children into creating chaos. Mandy decides not to share control of the world with Eris, and orders Grim to destroy the toys.