"Strike Witches" is set in an alternate version of Earth during the 1940s, where humanity faces an alien threat known as the Neuroi. These mysterious beings, resembling mechanical entities, have invaded and occupied large portions of the world, causing widespread destruction. To combat this threat, humanity develops advanced technology that combines magic and machinery, enabling individuals known as Witches to fight the Neuroi. Witches are young girls who possess magical abilities and are equipped with Striker Units, mechanical devices attached to their legs that allow them to fly and wield powerful weapons.

The story centers on the 501st Joint Fighter Wing, an elite unit of Witches assembled from various nations to defend against the Neuroi. The protagonist, Yoshika Miyafuji, is a kind-hearted and talented Witch from Fuso (an alternate version of Japan) who joins the 501st after being recruited by Major Mio Sakamoto, a veteran Witch and leader of the unit. Yoshika’s unique healing abilities and her connection to her late father, a scientist who developed the Striker Units, make her a valuable asset to the team.

The 501st operates from a base in Britannia (an alternate version of the United Kingdom) and engages in numerous battles against the Neuroi across Europe. Each member of the unit hails from a different country, bringing diverse personalities, combat styles, and magical abilities to the group. Key members include Lynette Bishop, a skilled marksman from Britannia; Perrine H. Clostermann, a proud and disciplined Witch from Gallia (an alternate France); and Francesca Lucchini, a carefree and energetic Witch from Romagna (an alternate Italy). The series explores their camaraderie, personal struggles, and growth as they face increasingly powerful Neuroi threats.

As the story progresses, the Witches uncover more about the Neuroi’s origins and motivations, leading to high-stakes confrontations that test their resolve and teamwork. The narrative balances action-packed aerial battles with moments of character development, highlighting the bonds formed within the 501st and their shared determination to protect humanity. The series also delves into the personal histories of the Witches, revealing how their pasts shape their roles in the fight against the Neuroi.

"Strike Witches" combines elements of military science fiction, fantasy, and historical inspiration, creating a unique setting where magic and technology intersect in a world at war. The series emphasizes themes of unity, sacrifice, and resilience, as the Witches confront both external enemies and internal challenges. Through its blend of action, character-driven storytelling, and imaginative world-building, "Strike Witches" presents a compelling narrative centered on the efforts of its diverse cast to defend their world from an overwhelming threat.