"Darker Than Black" is set in a world where mysterious phenomena have altered reality, creating anomalies known as Hell's Gate in Tokyo and Heaven's Gate in South America. These events led to the emergence of Contractors—individuals who gain supernatural abilities at the cost of a unique, often bizarre, price they must pay after using their powers. The story primarily revolves around Hei, a Contractor working as an assassin and spy for the Syndicate, a shadowy organization that manipulates Contractors for its own ends. Hei, also known as the "Black Reaper," is a highly skilled operative who conceals his true identity behind the guise of a mild-mannered Chinese exchange student named Li Shengshun.

The narrative unfolds in a morally ambiguous world where Contractors are treated as tools, and their humanity is often questioned. Hei's missions frequently bring him into conflict with other Contractors, government agencies, and rival organizations, all vying for control over the Gates and the secrets they hold. Alongside Hei are his companions, including Yin, a Doll—a being with limited emotions and the ability to remotely observe through water—and Huang, a former police officer who serves as Hei's handler. The group navigates a web of intrigue, betrayal, and shifting alliances as they uncover the truth behind the Gates and the origins of Contractors.

As the story progresses, Hei's past is gradually revealed, including his connection to his sister, Bai, who disappeared during the Heaven's Gate incident. The series explores themes of identity, morality, and the cost of power, as Hei struggles with his role as a Contractor and his desire to protect those he cares about. The plot is driven by a mix of episodic missions and overarching mysteries, culminating in a confrontation with the Syndicate and the revelation of the Gates' true nature. The narrative is characterized by its complex characters, intricate world-building, and a tone that balances action, suspense, and philosophical inquiry.