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.

In the near future, humans have discovered a fourth dimension, Dimension W, and a supposedly infinite source of energy within. In order to harness this profound new energy, mankind develops advanced "coils," devices that link to and use the power of Dimension W. However, by year 2071, the New Tesla Energy corporation has monopolized the energy industry with coils, soon leading to the illegal distribution of unofficial coils that begin flooding the markets. Kyouma Mabuchi is an ex-soldier who is wary of all coil-based technology to the extent that he still drives a gas-powered car. Kyouma is a "Collector," individuals with the sole duty of hunting down illegal coils in exchange for money. What started out as just any other mission is turned on its head when he bumps in Mira Yurizaki, an android with a connection to the "father" of coils. When a series of strange events begin to take place, these two unlikely allies band together to uncover the mysteries of Dimension W.

When Yun Arikawa and his partner, Haberu Katou, investigate a house rumored to be haunted, the last thing they expect is to stumble into a mystery that will soon envelop the entire planet. While measuring strange radio signals, they receive a call from Mei Kamino, a graduate student investigating the same signal and using the equipment their company previously installed. After an odd night, Yun returns to work at Ootaki Factory, a tech company that actually exists to produce Jet Jaguar—a robot that conspiracy theorist Gorou Ootaki has dreamed of creating. However, when flying dinosaur-like creatures known as Rodan are attracted to the strange radio signals, Jet Jaguar seems to be the only force capable of fighting them. As Yun and Mei investigate the Rodans' sudden appearance, more dangerous monsters begin to surface from the ocean—along with enigmatic red dust.

In a civilized society of anthropomorphic animals, an uneasy tension exists between carnivores and herbivores. At Cherryton Academy, this mutual distrust peaks after a predation incident results in the death of Tem, an alpaca in the school's drama club. Tem's friend Legoshi, a grey wolf in the stage crew, has been an object of fear and suspicion for his whole life. In the immediate aftermath of the tragedy, he continues to lay low and hide his menacing traits, much to the disapproval of Louis, a red deer and the domineering star actor of the drama club. When Louis sneaks into the auditorium to train Tem's replacement for an upcoming play, he assigns Legoshi to lookout duty. That very night, Legoshi has a fateful encounter with Haru, a white dwarf rabbit scorned by her peers. His growing feelings for Haru, complicated by his predatory instincts, force him to confront his own true nature, the circumstances surrounding the death of his friend, and the undercurrent of violence plaguing the world around him.