In the year 2021, a parasitic virus known as "Gastrea" infects humans and turns them into monsters. What is left of mankind now lives within the Monolith walls, walls that are made of Varanium, the only material that can hurt Gastrea. To counter the threat that the Gastrea pose, "Cursed Children"—female children whose bodies contain trace amounts of the virus which grant them superhuman abilities—officially called Initiators by the Tendo Civil Security, are given partners called Promoters, people who work to guide and protect the young Initiators. These teams of two are sent out on missions to fight the monsters created by the Gastrea virus and keep them at bay. Black Bullet revolves around the team of Enju Aihara, an Initiator, and Satomi Rentaro, a Promoter, as they go on missions to fight the growing threat of Gastrea in their hometown of Tokyo.

Although cheerful and delicate, Sakura Sakurakouji is a skilled martial artist with a sense of fairness that never falters—no matter the situation. Upon witnessing people burning in blue flames while on a bus ride home, she calls the police to bring their murderer to justice only to find that no evidence remains. However, all her doubts about what she saw vanish when the next day, the new transfer student Rei Oogami joins her class; he is the very boy she watched commit murder in cold blood. Rei is kind, sweet, and quickly becomes popular, contradicting Sakura's accusations. Soon enough, she learns his true nature: a Code Breaker, or "one who does not exist." To Sakura's shock, Rei—armed with mysterious powers—seeks to exact justice according to the principle of "an eye for an eye." Determined to bring Rei to the right path, Sakura keeps close to him in the hopes of redeeming him from his ways before others are hurt.

At the performing arts division of Seishou Music Academy, the ever-evolving stage threads the lives of its students together as they tirelessly hone their craft. Yet, as the girls prepare for a new rendition of the previous year's performance, the carefree Karen Aijou begins to settle for a smaller role. However, her waning passion is reignited by the return of her childhood friend Hikari Kagura, whose sudden transfer to the academy triggers a flurry of changes in the class dynamics. Subsequently, Karen chances upon a secret battleground underneath the school, which houses a set of auditions that will crown its ultimate victor as "Top Star." As she dives headfirst into these enigmatic trials, Karen begins to learn about the tribulations that come with vying for the top. Even if fate wills them apart, Karen and Hikari must fight in hopes of fulfilling their childhood promise: to become stars together.

The Four Cardinal Heroes are a group of ordinary men from modern-day Japan summoned to the kingdom of Melromarc to become its saviors. Melromarc is a country plagued by the Waves of Catastrophe that have repeatedly ravaged the land and brought disaster to its citizens for centuries. The four heroes are respectively bestowed a sword, spear, bow, and shield to vanquish these Waves. Naofumi Iwatani, an otaku, becomes cursed with the fate of being the "Shield Hero." Armed with only a measly shield, Naofumi is belittled and ridiculed by his fellow heroes and the kingdom's people due to his weak offensive capabilities and lackluster personality. When the heroes are provided with resources and comrades to train with, Naofumi sets out with the only person willing to train alongside him, Malty Melromarc. He is soon betrayed by her, however, and becomes falsely accused of taking advantage of her. Naofumi then becomes heavily discriminated against and hated by the people of Melromarc for something he didn't do. With a raging storm of hurt and mistrust in his heart, Naofumi begins his journey of strengthening himself and his reputation. Further along however, the difficulty of being on his own sets in, so Naofumi buys a demi-human slave on the verge of death named Raphtalia to accompany him on his travels. As the Waves approach the kingdom, Naofumi and Raphtalia must fight for the survival of the kingdom and protect the people of Melromarc from their ill-fated future.