"Nobunagun" is a 13-episode anime series that blends historical elements with science fiction and action. The story centers on Sio Ogura, a high school student with a deep fascination for military history, particularly the legendary Japanese warlord Oda Nobunaga. Sio's life takes a dramatic turn when she encounters a mysterious organization known as DOGOO (Defense Organization Global Officers), which recruits individuals capable of channeling the spirits of historical figures to combat extraterrestrial threats called "Evolutionary Invasion Objects" (EIOs).

Sio discovers she is a "E-Gene Holder," a rare individual who can manifest the powers of a historical figure. In her case, she inherits the abilities of Oda Nobunaga, gaining enhanced combat skills and the ability to wield a powerful weapon known as the Nobunagun. Alongside other E-Gene Holders, each embodying the spirits of notable historical figures like Jack the Ripper, Gandhi, and Newton, Sio joins DOGOO to protect humanity from the EIOs. The series explores her growth from an ordinary student to a determined warrior, balancing her personal struggles with her newfound responsibilities.

The narrative is driven by episodic battles against the EIOs, interspersed with character development and backstory revelations. Sio's interactions with her teammates, including the stoic Adam Muir (Jack the Ripper) and the enigmatic Geronimo (Gandhi), highlight themes of teamwork, sacrifice, and the weight of inheriting historical legacies. The plot escalates as the EIOs grow more formidable, culminating in a climactic confrontation that tests Sio's resolve and her connection to Nobunaga's spirit. The series concludes with a mix of resolution and open-ended possibilities, leaving room for further exploration of its unique premise.