"Strike Witches 2" continues the story of the 501st Joint Fighter Wing, a group of young girls known as Witches who possess magical abilities and use them to combat an alien force called the Neuroi. The series is set in an alternate World War II-era Europe, where the Neuroi have invaded and devastated much of the continent. The Witches, equipped with Striker Units—mechanical devices that enhance their magical powers—serve as humanity's primary defense against this extraterrestrial threat.

The narrative picks up after the events of the first season, with the 501st Joint Fighter Wing disbanded and its members returning to their respective homelands. However, the Neuroi resurgence forces the group to reunite. Yoshika Miyafuji, the protagonist and a skilled healer, initially hesitates to rejoin the fight due to personal conflicts and the loss of her mentor, Major Sakamoto. Despite her reservations, Yoshika eventually returns to the 501st, driven by her sense of duty and the bonds she shares with her comrades.

The series delves deeper into the personal struggles and backgrounds of the Witches, exploring themes of camaraderie, sacrifice, and resilience. Key characters include Lynette Bishop, a sharpshooter from Britannia; Perrine H. Clostermann, a proud and disciplined Witch from Gallia; and Mio Sakamoto, the seasoned leader of the 501st. Each character contributes uniquely to the team's dynamic, and their interactions highlight the challenges of balancing personal emotions with the demands of war.

As the Neuroi threat intensifies, the 501st faces increasingly formidable enemies, culminating in a climactic battle that tests their unity and resolve. The series maintains a balance between intense aerial combat sequences and quieter, character-driven moments, providing a well-rounded narrative. The conclusion ties up several storylines while leaving room for future developments, ensuring a satisfying yet open-ended resolution.