"Kemono Jihen" is a supernatural mystery anime set in a world where humans coexist with kemono, creatures that resemble mythical beings or animals. The story begins in a rural village where a boy named Kabane Kusaka works odd jobs while enduring ostracization due to his mysterious origins and unusual abilities. His life changes when Inugami, a detective specializing in kemono-related cases, arrives to investigate a series of strange incidents involving animal carcasses. Inugami recognizes Kabane's unique traits and invites him to Tokyo to work at his detective agency, which handles cases involving kemono.

In Tokyo, Kabane joins Inugami's team, which includes other kemono hybrids: Shiki, a reserved and intelligent boy with shadow manipulation powers; Akira, a cheerful and energetic fox kemono with illusion abilities; and Kon, a young girl with spider-like traits who struggles with her identity. Together, they tackle cases that often reveal the darker side of human-kemono interactions, uncovering conspiracies and confronting dangerous adversaries.

As the series progresses, Kabane learns more about his own origins, discovering that he is a rare type of kemono known as a "Dorotabo," a being born from the resentment of the dead. This revelation ties him to a larger conflict involving a secretive organization that seeks to exploit kemono for their own purposes. The narrative explores themes of identity, belonging, and the moral complexities of coexistence between humans and kemono, all while maintaining a balance of action, mystery, and character development.

The main characters' relationships and personal struggles are central to the story. Kabane's journey of self-discovery and his growing bond with his teammates form the emotional core of the series. Inugami serves as a mentor figure, guiding the group while harboring his own secrets. Shiki, Akira, and Kon each face challenges related to their kemono heritage, adding depth to their interactions and growth. The series blends episodic case-solving with an overarching plot, creating a cohesive narrative that keeps viewers engaged.