The rare and inexplicable Puberty Syndrome is thought of as a myth. It is a rare disease which only affects teenagers, and its symptoms are so supernatural that hardly anyone recognizes it as a legitimate occurrence. However, high school student Sakuta Azusagawa knows from personal experience that it is very much real, and happens to be quite prevalent in his school. Mai Sakurajima is a third-year high school student who gained fame in her youth as a child actress, but recently halted her promising career for reasons unknown to the public. With an air of unapproachability, she is well known throughout the school, but none dare interact with her—that is until Sakuta sees her wandering the library in a bunny girl costume. Despite the getup, no one seems to notice her, and after confronting her, he realizes that she is another victim of Puberty Syndrome. As Sakuta tries to help Mai through her predicament, his actions bring him into contact with more girls afflicted with the elusive disease.

Unlike many schools, attending Hyakkaou Private Academy prepares students for their time in the real world. Since many of the students are the children of the richest people in the world, the academy has its quirks that separate it from all the others. By day, it is a normal school, educating its pupils in history, languages, and the like. But at night, it turns into a gambling den, educating them in the art of dealing with money and manipulating people. Money is power; those who come out on top in the games stand at the top of the school. Yumeko Jabami, a seemingly naive and beautiful transfer student, is ready to try her hand at Hyakkaou's special curriculum. Unlike the rest, she doesn't play to win, but for the thrill of the gamble, and her borderline insane way of gambling might just bring too many new cards to the table.

The year is 2006, and the halls of Tokyo Prefectural Jujutsu High School echo with the endless bickering and intense debate between two inseparable best friends. Exuding unshakeable confidence, Satoru Gojou and Suguru Getou believe there is no challenge too great for young and powerful Special Grade sorcerers such as themselves. They are tasked with safely delivering a sensible girl named Riko Amanai to the entity whose existence is the very essence of the jujutsu world. However, the mission plunges them into an exhausting swirl of moral conflict that threatens to destroy the already feeble amity between sorcerers and ordinary humans. Twelve years later, students and sorcerers are the frontline defense against the rising number of high-level curses born from humans' negative emotions. As the entities grow in power, their self-awareness and ambition increase too. The curses unite for the common goal of eradicating humans and creating a world of only cursed energy users, led by a dangerous, ancient cursed spirit. To dispose of their greatest obstacle—the strongest sorcerer, Gojou—they orchestrate an attack at Shibuya Station on Halloween. Dividing into teams, the sorcerers enter the fight prepared to risk everything to protect the innocent and their own kind.

Mirai Kuriyama is the sole survivor of a clan of Spirit World warriors with the power to employ their blood as weapons. As such, Mirai is tasked with hunting down and killing youmu—creatures said to be the manifestation of negative human emotions. One day, while deep in thought on the school roof, Mirai comes across Akihito Kanbara, a rare half-breed of youmu in human form. In a panicked state, she plunges her blood saber into him only to realize that he's an immortal being. From then on, the two form an impromptu friendship that revolves around Mirai constantly trying to kill Akihito, in an effort to boost her own wavering confidence as a Spirit World warrior. Eventually, Akihito also manages to convince her to join the Literary Club, which houses two other powerful Spirit World warriors, Hiroomi and Mitsuki Nase. As the group's bond strengthens, however, so does the tenacity of the youmu around them. Their misadventures will soon turn into a fight for survival as the inevitable release of the most powerful youmu, Beyond the Boundary, approaches.