"Devil Hunter Yohko" centers on Yohko Mano, a high school girl who discovers she is the 108th successor in a lineage of Devil Hunters, a role she initially resists. The series begins with Yohko’s ordinary life being disrupted when she learns of her destiny to battle demons threatening the human world. Her grandmother, Madoka Mano, reveals the family’s ancient duty and trains Yohko to wield the sacred sword, Raiden, essential for defeating demons. Despite her reluctance, Yohko is thrust into the role after her grandmother’s death, inheriting the responsibility to protect humanity.

The narrative follows Yohko’s journey as she confronts various supernatural threats, often tied to her family’s history. Alongside her is Azusa, a cheerful and loyal friend who provides emotional support, and Chiaki, a mysterious and skilled Devil Hunter who becomes a rival and occasional ally. The series explores Yohko’s growth as she balances her personal life with her duties, facing increasingly dangerous adversaries. Key antagonists include demons seeking to exploit her inexperience, as well as figures from her family’s past who challenge her resolve.

The plot is episodic, with each arc focusing on a specific demon or supernatural event, while gradually revealing the broader mythology of the Devil Hunters. Themes of duty, legacy, and self-discovery are central, as Yohko grapples with her identity and the weight of her inherited role. The series blends action, comedy, and supernatural elements, with Yohko’s determination and evolving skills driving the narrative forward. Her journey culminates in a climactic battle against a powerful demon, testing her abilities and resolve as the 108th Devil Hunter.