Two years have passed since the CCG's raid on Anteiku. Although the atmosphere in Tokyo has changed drastically due to the increased influence of the CCG, ghouls continue to pose a problem as they have begun taking caution, especially the terrorist organization Aogiri Tree, who acknowledge the CCG's growing threat to their existence. The creation of a special team, known as the Quinx Squad, may provide the CCG with the push they need to exterminate Tokyo's unwanted residents. As humans who have undergone surgery in order to make use of the special abilities of ghouls, they participate in operations to eradicate the dangerous creatures. The leader of this group, Haise Sasaki, is a half-ghoul, half-human who has been trained by famed special class investigator, Kishou Arima. However, there's more to this young man than meets the eye, as unknown memories claw at his mind, slowly reminding him of the person he used to be.

Goblins are known for their ferocity, cunning, and rapid reproduction, but their reputation as the lowliest of monsters causes their threat to be overlooked. Raiding rural civilizations to kidnap females of other species for breeding, these vile creatures are free to continue their onslaught as adventurers turn a blind eye in favor of more rewarding assignments with larger bounties. To commemorate her first day as a Porcelain-ranked adventurer, the 15-year-old Priestess joins a band of young, enthusiastic rookies to investigate a tribe of goblins responsible for the disappearance of several village women. Unprepared and inexperienced, the group soon faces its inevitable demise from an ambush while exploring a cave. With no one else left standing, the terrified Priestess accepts her fate—until the Goblin Slayer unexpectedly appears to not only rescue her with little effort, but destroy the entire goblin nest. As a holder of the prestigious Silver rank, the Goblin Slayer allows her to accompany him as he assists the Adventurer's Guild in all goblin-related matters. Together with the Priestess, High Elf, Dwarf, and Lizardman, the armored warrior will not rest until every single goblin in the frontier lands has been eradicated for good.

Tomoya Okazaki and Nagisa Furukawa have graduated from high school, and together, they experience the emotional rollercoaster of growing up. Unable to decide on a course for his future, Tomoya learns the value of a strong work ethic and discovers the strength of Nagisa's support. Through the couple's dedication and unity of purpose, they push forward to confront their personal problems, deepen their old relationships, and create new bonds. Time also moves on in the Illusionary World. As the plains grow cold with the approach of winter, the Illusionary Girl and the Garbage Doll are presented with a difficult situation that reveals the World's true purpose.

Ainz Ooal Gown, the undead sorcerer formerly known as Momonga, has accepted his place in this new world. Though it bears similarities to his beloved virtual reality game Yggdrasil, it still holds many mysteries which he intends to uncover, by utilizing his power as ruler of the Great Tomb of Nazarick. However, ever since the disastrous brainwashing of one of his subordinates, Ainz has become wary of the impending dangers of the Slane Theocracy, as well as the possible existence of other former Yggdrasil players. Meanwhile, Albedo, Demiurge and the rest of Ainz's loyal guardians set out to prepare for the next step in their campaign: Nazarick's first war… Overlord II picks up immediately after its prequel, continuing the story of Ainz Ooal Gown, his eclectic army of human-hating guardians, and the many hapless humans affected by the Overlord's arrival.