"Black Bullet" is set in a dystopian future where humanity faces extinction due to parasitic creatures known as Gastrea. These monsters emerged in 2021, spreading a deadly virus and forcing humans to retreat into heavily fortified cities. The Gastrea are highly resistant to conventional weapons, leading to the development of specialized weapons called Varanium, which can harm them. To combat the threat, children known as Cursed Children, who are infected with the Gastrea virus but retain human consciousness, are paired with Promoters, adult handlers, to form teams called Civil Security Officers. These teams are tasked with protecting the cities from Gastrea incursions.

The story centers on Rentaro Satomi, a young Promoter, and his partner Enju Aihara, a Cursed Child with enhanced physical abilities. Rentaro is driven by a strong sense of justice and a desire to protect humanity, while Enju, despite her tragic circumstances, remains cheerful and loyal. Together, they work as Civil Security Officers in Tokyo Area, undertaking missions to eliminate Gastrea threats and maintain order. Their partnership is tested as they uncover deeper conspiracies involving the government, the origins of the Gastrea, and the treatment of Cursed Children, who are often ostracized and exploited by society.

As the narrative progresses, Rentaro and Enju encounter other key characters, such as Kisara Tendo, Rentaro’s childhood friend and the head of the Tendo Civil Security Agency, and Tina Sprout, a skilled assassin and Cursed Child who initially opposes them. The story explores themes of discrimination, survival, and the moral complexities of a world on the brink of collapse. The characters face escalating challenges, including internal conflicts within the government, betrayals, and the constant threat of Gastrea mutations. The series balances action-packed battles with emotional moments, highlighting the bonds between Promoters and Cursed Children while delving into the harsh realities of their world.