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. In the present, Grim goes to reap General Skarr, who accidentally got a big wound in his torso. However, due to Billy and Mandy's meddling, Skarr escapes, and they make a big mess in the city. Following his failure to be an effective Reaper, Grim is taken to the Underworld Court, presided by Judge Roy Spleen, where he is sued for misuse of his powers by his nemesis, the Boogeyman. After the trial, Grim is found guilty, is stripped of his rank and magical scythe, and he, Billy, Mandy, and Irwin are sentenced to be exiled. Then, Boogey volunteers to carry on the sentence by taking the prisoners aboard his ship, and dropping them off in a river of fire; he plans to do t

On a rainy day, several 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 doesn't figure it out until he receives a message saying that Velma, the Spider Queen, an old friend from high school, is responsible for it. Meanwhile, Billy meets with his "son", 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. Upon meeting in the school's football field, Velma tells Grim that she has finally come to devour his skull and absorb his powers, since one hundred thousand years ago Grim cheated and robbed her from the possibility of becoming the Reaper. Converting the school into her own palace, and with help from the Dark Elves, Velma captures Mandy, Mindy, and Grim, and proceeds to devour the latter's skull. However, when Velma cracks

Billy, Irwin and Mandy go trick-or-treating on Halloween, and an evil marshmallow bunny attacks children with chocolate beasts.

While Billy's Dad is underwear shopping, Billy wears his dad's lucky pants, and accidentely rips them with Grim's scythe. He calls Ed, Edd n Eddy, and they recommend Kids Next Door for charity. Numbah 1 disguises as Billy while Billy is taken back to the Deep Sea Lab. Mandy arrives at Billy's house and knows Numbah 1 is not Billy, and tortures him into revealing the truth. Meanwhile, the Delightful Children From Down the Lane and Billy accidentely fuse with the scythes power to create the Delightful Reaper. Mandy takes over the KND by fooling Numbah 363 and the rest of the KND, but Numbah 5 knows she's not Numabh 1, but is taken to the med lab. The Delightful Reaper assimilates nearly all of Endsville (including Numbah 2) and grows more powerful. Numbah 1 and Grim try to get the KND to see sense but are imprisoned. Numbah 5 escapes and finds Numbah 1 and Grim. Grim and Numbah 1 fuse with the Bone of Barnacles and become the Skeleton Samurai. Mandy in her Mandrobot (Monkeys And Nice Dog

Billy looks into Grim's trunk and sees a monster and names it Myron. But when Billy brings Myron outside to his backyard, he gets eaten in the end.

In 2007, Cartoon Network released a short based off of The Grim Adventures of Billy & Mandy titled Matinee Mandy. It is unknown as to what specific date the short was released or if it even aired in America at all. Two versions of the short are known to exist online, both uploaded to YouTube, but neither is in English. The first upload is in 4:3 and features both Chinese subtitles and Chinese voices. The second upload is in widescreen; it appears to be a partial recording from a Thai version of Boomerang and features Thai dubbing. It is unknown if the English version was ever released or if any copies of it still exist. In May of 2017, YouTube user shooterboss uploaded the Chinese dub with fan-made English subtitles.

Billy, Mandy and Grim try to save Christmas when vampires invade Santa's workshop in the North Pole.