In a world besieged by mysterious alien creatures known as Savages, humanity has developed advanced weapons called Hundred, which are the only effective means of combating these threats. The story centers on Hayato Kisaragi, a young man who enrolls at Little Garden, a prestigious academy training Slayers—individuals capable of wielding Hundred. Hayato possesses a unique ability to synchronize with his Hundred at an exceptionally high rate, making him a rare and valuable asset in the fight against the Savages.

Upon arriving at Little Garden, Hayato reunites with his childhood friend, Claire Harvey, who harbors strong feelings for him. Claire is a skilled Slayer and a member of the student council, often finding herself in competition with Emilia Gudenberg, a noble and powerful Slayer from a prestigious family. Emilia initially clashes with Hayato due to her pride and distrust of outsiders, but their relationship evolves as they face challenges together. The trio forms a dynamic partnership, balancing personal rivalries with their shared mission to protect humanity.

As the narrative progresses, Hayato and his peers confront increasingly dangerous Savages while uncovering secrets about the origins of these creatures and the true nature of the Hundred. The story delves into themes of camaraderie, sacrifice, and the moral complexities of wielding power. Hayato’s past is gradually revealed, including his connection to a mysterious girl named Sakura Kirishima, who plays a pivotal role in the unfolding events. The series combines action, romance, and science fiction elements, exploring the personal growth of its characters as they navigate the challenges of their roles as Slayers and the broader conflict against the Savages.