"Zero Kara Hajimeru Mahō no Sho" is a fantasy manga series set in a world where humans and witches coexist, though witches are often persecuted and feared. The story revolves around a witch hunter known as Zero and a half-beast mercenary named Mercenary. Zero is a powerful witch who seeks to reclaim a magical tome called the "Book of Zero," which contains immense power and knowledge. The book was stolen from her, and she enlists Mercenary's help to retrieve it. Despite his initial reluctance, Mercenary agrees to assist her in exchange for her lifting a curse placed upon him.

The narrative unfolds as the two travel together, encountering various challenges and adversaries. Zero is a stoic and enigmatic figure, possessing vast magical abilities but often relying on Mercenary's combat skills and resourcefulness. Mercenary, on the other hand, is pragmatic and cynical, shaped by his experiences as a half-beast outcast. Their dynamic evolves from a transactional partnership to a deeper bond as they face dangers and uncover secrets about the world and themselves.

Throughout their journey, they confront witch hunters, rival witches, and other supernatural entities, all while piecing together the mysteries surrounding the Book of Zero. The story explores themes of prejudice, identity, and the consequences of wielding power. The world-building incorporates a blend of medieval and fantastical elements, with a focus on the tension between humans and witches. The manga balances action, intrigue, and character development, offering a layered narrative that delves into the complexities of its protagonists and the world they inhabit.