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.

Lord Pain, a fearsome warrior from the Plain of Eternal Suffering, appears in Billy's house looking to serve his master, Grim. Lord Pain is put to clean the bathroom, and is confused as to why Billy and Mandy treat Grim the way they do. Eventually, Lord Pain realizes that Mandy is to be his real master, and prepares mashed potatoes for her.

When Billy, Mandy and Grim go playing golf, they encounter boy wizard Nigel Planter again, who is there hiding from the dark wizard Lord Moldybutt. They head back to the School of Sorcery, where they keep on running into Moldybutt, who warns them to stay away from the "Chamber Pot of Secrets" hidden in Dean Toadblatt's office. It is revealed that Lord Moldybutt is actually Toadblatt, who was disguising himself to scare off Planter. Note: The title is a spoof of Harry Potter and the Chamber of Secrets.

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.

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.

When Billy jumps into a supernatural puddle (a Cosmic Sinkhole, according to Grim), it takes him to the home of Granny Applecheeks, who wants to bake him into a pie. It is up to Mandy and Grim to save him if the puddle can take them to the right place.

After Grim's scythe fails to open a portal, he decides to sharpen it, but the blade breaks. Billy, Mandy and Grim go to the Underworld to meet F (a parody of James Bond's "Q"), who is in charge of the Underworld secret gadgets. F unveils Scythe 2.0, which is a new-and-improved sentient, autonomous, thinking and feeling computerized scythe, that Grim uses while his classic scythe is being repaired. When Mandy tells Grim to do his usual humiliating chores, Grim delegates the work to Scythe 2.0, which rebels and decides to reap by itself, starting with Billy and Mandy. Grim saves the kids, takes Scythe 2.0 back to the Underworld, and returns with his old scythe.

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 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.

When Billy gets his kite stuck in a tree, he starts throwing objects at it to knock it down, including Mandy and a group of three boy scouts, but all objects get stuck too. Frustrated, Billy and Grim call a druid for help, who in turn trains them to become druids, so the three of them can perform a ritual. Meanwhile, inside the tree, Mandy battles a group of squirrels, and leads the scouts back to the ground. Since the druidic chants did not work against the tree, the druid goes ahead and uses a chainsaw to bring the tree down, but this gets him arrested.

When Mandy and Grim go to the warehouse store, Mandy notices that everything seems to be in order, lacking any presence of chaos. Hoss Delgado, spectral exterminator, arrives saying that everything has been that way since he started dating Eris, the goddess of chaos. Mandy assures Delgado he must break up with Eris to restore chaos, but fearing her temper, he is reluctant to do so. After failed attempts by Grim, Mandy, Billy, and Irwin to break their relationship, Delgado finally tells Eris the truth about he wanting to break up, and she complies by turning into a giant insect and devouring him.

As Billy behaves more reckless than ever and cannot stop breaking everything in sight, Mandy thinks he should go some place where he can release all his urge to destroy until he gets tired of it. Mandy, Grim, and Irwin go to Level 9, home of the fearsome warrior Lord Pain, to convince him to take Billy. Billy receives psychological treatment and it is revealed that his desire to destroy stems from lack of attention when he was younger. Lord Pain abducts him, and together they start destroying everything in Level 9, which seems to be is uninhabited. Billy is still not satisfied, so he and Lord Pain return to Endsville and carry on breaking everything.

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 Nergal comes to tell the guys about his new pizza joint, Grim thinks he can do better by using his Granny's recipe. A pizza war ensues between Nergal's Pizza and Grim's Pizza, with each pizzeria launching TV ads and discrediting each other. Nergal Jr. uses his shape-shifting abilities to infiltrate Grim's pizza and replace Granny Grim's hot sauce with a "ghastly elixir". The result is pizzas becoming monsters and attacking the city, and the citizens developing parasites similar to Nergal. Nergal and his family leave the city just as Grim's sauce explodes.

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.