"Owari no Seraph" is set in a post-apocalyptic world where a mysterious virus has wiped out most of humanity, leaving only children under the age of 13 alive. In the aftermath, vampires emerge from the shadows and establish a feudal system, enslaving the remaining human population as livestock. The story centers on Yuichiro Hyakuya, a young boy who loses his family to the virus and is subsequently captured by vampires. Alongside other orphaned children, including his close friend Mikaela Hyakuya, Yuichiro is raised in a vampire-controlled city, where humans are treated as subservient beings.

Yuichiro harbors a deep hatred for vampires and dreams of one day escaping and exacting revenge. During a failed escape attempt, Mikaela sacrifices himself to ensure Yuichiro's survival. This event becomes a driving force for Yuichiro, who vows to destroy all vampires. He is later rescued by the Japanese Imperial Demon Army, an organization dedicated to eradicating vampires and reclaiming the world for humanity. The army employs cursed gear—weapons infused with demonic power—to combat the vampires, who possess superhuman strength and abilities.

Yuichiro joins the Demon Army and trains to become a skilled soldier, forming bonds with fellow recruits, including Shinoa Hiragi, Yoichi Saotome, and Kimizuki Shiho. Together, they form a squad tasked with combating vampire threats. As the story progresses, Yuichiro's resolve is tested when he discovers that Mikaela is still alive but has been turned into a vampire. This revelation creates a moral dilemma, as Yuichiro must reconcile his hatred for vampires with his lingering affection for Mikaela.

The narrative explores themes of loyalty, revenge, and the blurred lines between humanity and monstrosity. The vampires, led by figures such as Ferid Bathory and Krul Tepes, are portrayed as complex antagonists with their own motivations and hierarchies. The Demon Army, while ostensibly fighting for humanity's survival, is also shown to have its own dark secrets and internal conflicts. The series delves into the origins of the virus, the true nature of the demons powering the cursed gear, and the history of the vampires' rise to power.

As Yuichiro and his squad engage in battles against both vampires and rogue human factions, the story gradually reveals a larger conspiracy involving ancient beings and the potential for humanity's extinction. The characters' relationships and personal struggles are interwoven with the overarching plot, creating a balance between action-driven sequences and emotional depth. The series combines elements of dark fantasy, military strategy, and moral ambiguity, making it a compelling exploration of survival and identity in a fractured world.