Billy and Mandy take a reluctant Grim to school with them. Mandy's nemesis, Mindy, befriends Grim to annoy Mandy, and Billy calls for their other friend, who is Abraham Lincoln. Mandy devises a plan in which Mindy ditches Grim, and keeps Abraham as her friend instead.

Grim is lying sick in bed with "Encroaching Doom Syndrome". The Underworld doctors are not able to help Grim, and he becomes a human being. Back in Endsville, Grim seems attractive to women, but he ends up being punched by jealous boyfriends, especially Billy's dad Harold. Grim covers himself in the mucus that he produced when he was sick and becomes a skeleton again, and Billy tries it too.

After being accidentally hit by Billy, Grim lands in a can of white paint in a remote convent. Due to his appearance, still with the can in his head, Grim is mistaken for "Sister Big Mamma" by little nuns. Grim has a great time with the friendly nuns, until Billy and Mandy come looking for him. When the nuns realize the truth about Grim they get angry at him, but also help him go back home by sending him flying away with another punch.

After being impressed by Irwin's realistic armor at the medieval fair, Billy wishes for a fancy armor too. Grim gives him the "Cursed Suit of the Black Knight". When Billy needs to go to the bathroom, the curse is revealed to be that the armor cannot be taken off until the person wearing it beats someone in a competition. Billy desperately tries to defeat other people at various contests, he but fails to come out victorious. He defeats Mandy at a breakdance contest in which Mandy decided not to participate, but he does not need to go to the bathroom anymore.

Grim's refusal to help Mandy win a karate tournament, and the $50,000 prize it promises to the winner, leads her to a curio shop, where the shopkeeper, Kuan Ti, gives her an ancient "Chicken Ball" which, when eaten, allows her to become a great fighter. Mandy easily wins the tournament and does not care about the money anymore, only about fighting. It turns out Kuan Ti is actually Eris in disguise, and this was just another of her schemes to create chaos. Seeing how he has a chance to get rid of the kids and finally be free, he tries to take advantage over this by making Billy a superb fighter too, so he and Mandy can fight ferociously to the death until the entire arena is destroyed. With both still alive, Mandy still demands the prize money, which she uses to buy Hector Con Carne's Bunny Island.

Billy, Mandy and Grim go trick-or-treating for Halloween, and Irwin is left behind because he needs a scarier costume. After pulling a trick on an old lady, and getting some candies, Grim tells the story of why people pull pranks, which he was partially responsible for.

It's Valentine's Day and Nergal, the fiend living in Earth's core, appears in Billy's house to court Billy's spinster aunt Sis. Billy tries ruining Nergal's date, to avoid becoming his nephew. Although initially Sis does not show interest in Nergal, she changes her mind when Nergal is stung by bees and she sees his "dance moves". Aunt Sis accepts Nergal's marriage proposal and accompanies him back to the center of the Earth.

After spilling salt in a restaurant, and not throwing salt over his left shoulder, Billy starts having an unusual amount of extremely bad luck. The next day, Grim analyzes Billy and finds out he has a "Catastrophe Snail" attached to his brain, which is causing him the bad luck.

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.

When Billy ruins his eyes by playing too many video games and looking directly into the Sun, Mandy and Grim suggest he see an ophthalmologist. When Billy refuses wearing glasses or having laser surgery, Grim uses his own scythe to zap his eyes. Although Billy has sharp and clean eyesight, he can also see glimpses of the future, specially horrific accidents that occur to his best friends. Grim zaps Billy's eyes multiple times to restore them to normal. Billy ends up with weird-looking eyes.

After failing to scare a fifteen-year-old, the Boogeyman decides to visit his old middle-school victim, Grim. Grim remembers how Boogie used to be a bully, and demands an apology from him. Boogie disappears to the Underworld, taking Billy with him. Mandy and Grim follow Boogie, and to settle their differences Mandy suggests having a scaring contest, in which whoever can scare a kid the most wins. Boogie's transformation as a werewolf is not enough to scare the kid, but Grim's transformation into a giant, horrific rubber duck is.

After watching a TV show, starring Captain Heifer and his Heifer Farms Brand Yogurt, Billy asks Grim to turn him into a superhero with the power of squeaking and throwing yogurt from his armpits. With his wish granted, Billy goes to outer space to fight the Evil Empire, but the planet he visits is mostly inhabited. Despite being free of Billy, Grim still has to deal with Billy's equally dumb father, Harold. After Billy fills the alien planet with yogurt, he returns home to be "normal".

During a thunderstorm, a lightning bolt hits Grim's scythe, transporting Billy to Asgard, land of the Norse gods. Mandy and Grim go searching for him, while a Viking wearing Billy's shirt remains at his house as a substitute. In Asgard, Billy learns about the endless battle in Valhalla, in which if a warrior dies, he is resurrected to continue fighting. Billy is surprisingly good at killing other Vikings, so Mandy and Grim are unable to convince him to return home.

Grim is annoyed by Billy who thinks that a shadow is following him. Grim takes Billy and Mandy to the Shadows' World, where their opposites live. Grim tells them to do whatever they want, but to be back at 5 o'clock, when the portal to the normal world opens. Grim also warns Billy about the Door to Other Dimensions, but Billy opens it and a multitude of Billys come out an wreak havoc.

When Billy has a loose tooth he cannot wait for the Tooth Fairy to appear to give him money. Mandy, who does not believe in the Tooth Fairy, asks Sperg to end Billy's waiting by knocking his tooth off. Sperg's punch leaves Billy unconscious, who has a dream about being in the wild west, where the Tooth Fairy has taken his tooth. Mandy challenges the Tooth Fairy to a showdown to recover the tooth, and she comes out victorious just as Billy awakens. Billy does find money under his pillow, while the aged Tooth Fairy watches through the window.

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 and Mandy's school is preparing for a big game, Mindy entrusts the care of the school's mascot, Fluffy Cat, to Billy, to protect him from being kidnapped by the rival team, the Booty Heads. At Billy's house, Fluffy Cat is a disaster, so Billy's mom throws him into the basement, where the cat gets inside Grim's trunk, absorbing its powers. A giant Fluffy Cat appears just before the game wreaking havoc.

When Billy goes into the mud for the fifth time in the day while wearing his white tuxedo before a wedding, Grim tries to figure out why Billy is so stupid. Billy's dad recounts Billy's life from his birth until he met Mandy and explains that Billy is not dumb, but actually a genius with a certified "Honorary Genius Degree". It is quite evident to Grim that Billy's problem is his equally dumb father.

After Grim's robe comes out of the washing machine, Billy and Mandy find Thromnambular, a talking skull with ruby eyes and a number nine imprinted on his forehead. Grim tells them that the skull is a magical artifact imprisoned on Earth that must grant his nine wishes to be free. When Mandy asks Grim why he has not used any of the wishes, Grim tells her that the skull will corrupt the wishes and end up affecting the wisher.

After Grim has a nice dream, a nightmare escapes the back of his head in the shape of a supernatural, invisible duck that makes farting noises. The duck follows Grim everywhere, causing him embarrassment with the non-existent farts, and to end up in jail. The duck repeats the strategy, following other citizens, including Irwin and Billy's dad, resulting in all of them going to jail too. The duck tries to annoy Mandy, but she remains imperturbable by its presence. The duck disappears and Principal Goodvibes is really angry, and he gives Mandy 75 days of detention.

Billy and Mandy find a supernatural zipper from Grim's robe, and while Billy uses it to create mischief, Mandy gets herself in a sticky situation.

When it's scurvy-prevention day at school, Mindy parades in her float in anticipation for the Little Miss Scurvy beauty pageant, and she insults Mandy, telling her she is ugly. To prove her otherwise, and with Principal Goodvibes' encouragement, Mandy considers entering the pageant. Naturally, Billy and Grim cannot believe Mandy when she tells them about the idea, but finally they decide to help her. Grim calls for Crabina, the Underworld's greatest makeup artist, to give Mandy a complete makeover. Crabina is shocked by Mandy's sour attitude, so she sets up principally to make her smile. At the pageant, Mandy has a real chance at winning the contest, but she still refuses to smile during her heart-warming musical number. Ultimately she smiles, but this event is so powerful that it alters the laws of the universe, and The Grim Adventures universe transforms into the The Powerpuff Girls universe, with Billy, Mandy and Grim turning into the Powerpuff Girls, Irwin turning into Mojo Jojo, and Professor Utonium guest starring as himself in a brief speaking cameo.

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.

When Billy, Mandy and Grim notice things have been disappearing in the house, they set out to investigate using a supernatural detector. They find the culprit is a talking "taking tree" in Billy's yard, who has been stealing objects since Billy's dad was a child. To make the tree happy, Mandy and Grim set out to trade the stolen belongings for a highly-valued Mickey Munchle baseball card, which is worth eleventy million dollars. Mandy and Grim return from the baseball shop with the real Mickey Munchle. The tree returns all of the stolen things, but keeps the player.

When Billy and Irwin start making prank calls, everybody knows that Billy is behind the calls because every telephone has a caller ID. While Billy searches in Grim's trunk in the basement for something to defeat the caller ID, he finds a skull-shaped phone with no caller ID. Grim warns him to not use the phone, because it is used to call the ancient demon Cthulhu, whose sole appearance makes people go mad, and if awakened will cause the destruction of the world. Despite Grim's warning, Billy and Irwin use the phone anyway, and they are sucked into it by tentacles.

The day before Christmas, Billy, Mandy and Grim go to the shopping mall, where Mandy complains that Santa Claus is just an invention from corporations. Grim assures Mandy that Santa is real, and they even went to college together. They decide to travel to the North Pole and meet Santa, but when they arrive Mrs. Claus tells them that Santa Claus has been transformed into a vicious vampire.

When Billy, Mandy and Grim go to the beach, Billy is swallowed by a whale known as Blubbery Joe, which also houses in her stomach Mister Geppetto and Pinocchio. Tired of not having a real son, Geppetto convinces Billy to be his "real son", while Pinocchio becomes increasingly jealous and is set on eating Billy's flesh to become a real boy and gain Geppetto's fatherly love and affection. Mandy and Grim search for Billy on board Captain Deadwood's ship, who is made of wood and who has been hunting Blubbery Joe for years. Billy, Geppetto and Pinocchio are expelled from Blubbery Joe's stomach, and as Billy needs to go home, Blubbery Joe accepts to be Geppetto's son.

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 destroys Grim's favorite childhood toy, Fancy Jake, Grim feels devastated and wishes he had never lost the limbo game that made him become Billy and Mandy's best friend forever and ever. A lawyer appears saying that although the game is legally binding while all parties remain on Earth, it is not if Grim leaves Earth. In consequence, Grim follows the lawyer's advice, opens a mystical portal, and leaves. With Grim traveling aboard his spaceship, the lawyer takes off his disguise and introduces himself as Morg, the Martian Grim Reaper, who is also Emperor of Mars and commands an army of Martian, brain-eating zombies.

When Grim decides to visit again his childhood idol, the aged king of the vampires, Dracula, the latter suggest they drive to an early bird buffet, only to get lost in the scorching desert. Grim and Dracula need to find their way back home while dealing with situations like meeting a creepy truck driver and being attacked by a giant scorpion. After what they have gone through, and thinking that Dracula is just a selfish, old man, Grim decides to go a separate way. After finding that Dracula in fact helped him by sucking out the scorpion's venom, Grim rushes to help Dracula, and they finally make it to the diner. However, it appears that Dracula left without paying the check.

When Billy desperately wants chewing gum at school, Grim gives him a bottomless gumball machine, but warns him not to swallow the gum. Billy ignores Grim's warning and starts swallowing the gum, causing him to constantly burp bubbles that fill the entire city. Mandy and Grim try to get Billy to cough the remaining gum that he has in his stomach, but instead Billy swallows the entire gumball machine. Billy coughs huge amounts of gum all over the city and ends up with a supernatural rash from another interdimensional world.

At a school fair, Grim's scythe accidentally transforms the dull Principal Goodvibes and his hippopotamus into gangster rappers, Goodvibes now calling himself Principal Goodbling. In the following, Goodbling changes the entire school to be more hip-hop-oriented, to the annoyance of Mandy. Although initially Grim likes the new style of the school principal, he later thinks Goodbling is just a poseur and goes to talk to him, but Goodbling attacks with yo-mama jokes. Irwin's grandmother, Tanya, confronts Goodbling and proves to be better than he is at yo-mama jokes that Goodbling reverts to being the boring Goodvibes.

As Billy, Mandy, Grim, and Irwin hang from a rope about to be eaten by a giant sea serpent, Irwin wonders how they came into that trouble. Billy and Grim each tell separate stories on how they originally became best friends forever and ever. Billy's fantastic story is about him and Mandy being space patrol officers who collect the Grim Reaper's bones, cloak, and skull to summon him; Grim tells a story on how the evil Mandy and his pet servant Billy managed to capture him inside a containment unit (parodying the Ghostbusters' ghost traps). Mandy quickly tells the real story, and footage from the first episode is seen, before the four are swallowed whole by the serpent.

When Mandy finds Billy playing with Grim's gigantic dog, Cerberus, she tells Grim to keep Billy under tight control because she needs a good night of sleep to be ready for the next day's test. With a little persuasion from his own dad, Billy tries to wake up Mandy at night, so she will fail the test and he can score higher than her for the first time. After Grim spends the night guarding Mandy's house from Billy, the latter succeeds in waking up Mandy. It is revealed that this Mandy is in fact Irwin, used as a decoy by the real Mandy, who slept in her dog's house. Mandy passes the test, and Grim is punished for not guarding her properly.

When Billy, Mandy and Grim once again go to the beach, Grim warns Billy to avoid swimming too far, because the "undertoad", a frog-like creature, will try to drag him into the sea. Billy encounters the undertoad, and he barely makes it back to the beach. With the dangers of the sea averted, the guys go back home, but the undertoad is set on bringing Billy down, that he follows him to his house. The next day, the undertoad becomes a constant annoyance to Billy, even at school. Grim and Mandy capture the undertoad, and set sail to release him at sea, where they meat the giant Mama undertoad.

A scene of Endsville two weeks into the future shows a dystopian world ruled by the "Lord of Horror", who wields the all-powerful artifact known as "Horror's Hand". At the same time, two robotic replicas of Billy and Mandy are sent into the past, to stop the real Billy and Mandy from interfering with the current events.orror's Hand to rule the world.

When Billy is sent to bed after playing with his Dr. Brainiac action figure, he wishes he had an adventure. He notices a strange light outside and wanders into a corn field to investigate; he encounters Sperg, and both of them got caught by a UFO's tractor beam. Inside the extraterrestrials decide to experiment on them.

On a rainy day, giant spiders appear in Billy and Mandy's school and start kidnapping the children one by one. Grim presumes this is somehow related to his past, but does not figure it out until he receives a message saying that Velma, the Spider Queen, an old good friend from high school, is responsible for it. Meanwhile, Billy meets with Jeff the Spider, who informs him that he is precisely marrying Velma. After trying to recover a talking carton of chocolate milk from Jeff, Billy and Jeff get into a fight, and Jeff looks angrier than ever before.

When vampire hunter Lionel Van Helsing prepares to kill Dracula, Billy, Mandy, and Grim arrive to stop him since Dracula is just senile and harmless. Van Helsing reveals the source of his hatred: in the past, he and Dracula were "best friends forever", until Dracula used his irresistible dance moves to marry Tanya, the woman of his dreams. Tanya arrives too, revealing that she is none other than Irwin's grandmother, making Irwin one-quarter-vampire on his father's side and half-mummy on his mother's side. Van Helsing leaves, but Dracula is unsatisfied with his newfound family of nerds.