"Kakumei Kyōshitsu" is set in a dystopian future where humanity faces extinction due to the emergence of a powerful alien species known as the "Horrors." These creatures, led by the enigmatic and seemingly invincible being called Shiro, have driven humanity to the brink of annihilation. In response, the remnants of human society have established a militarized education system designed to train the next generation of leaders and warriors to combat the Horrors. The story centers on Class 3-E of Kunugigaoka Middle School, a group of students deemed the "worst" in the school and assigned to a dilapidated classroom on a mountain. Their teacher is none other than Shiro, who, after destroying the moon, has inexplicably taken on the role of their educator. Shiro offers the students a deal: if they can assassinate him within a year, they will receive a substantial monetary reward. However, if they fail, he will destroy Earth.

The students, initially skeptical and fearful, gradually come to understand Shiro's unique teaching methods. Despite his alien nature and immense power, Shiro proves to be a dedicated and effective teacher, fostering both academic growth and personal development among the students. He encourages them to harness their individual strengths and work together, transforming the class from a group of outcasts into a cohesive unit capable of facing the challenges ahead. The narrative explores the students' struggles, growth, and relationships as they navigate their dual roles as students and assassins. Each student has a distinct personality and backstory, contributing to the class's dynamic and the overarching plot. Key characters include Nagisa Shiota, a quiet and observant boy who becomes a skilled strategist; Karma Akabane, a rebellious and highly intelligent student with a knack for combat; and Kaede Kayano, a cheerful and determined girl with hidden depths.

As the story progresses, the students uncover deeper mysteries surrounding Shiro's true intentions and the origins of the Horrors. They face numerous obstacles, including rival classes, government interference, and internal conflicts, all while preparing for their ultimate goal of assassinating Shiro. The series balances action, humor, and emotional depth, with themes of perseverance, camaraderie, and the complexities of morality. The interplay between the students' personal growth and their mission to save humanity drives the narrative forward, culminating in a climactic confrontation that challenges their resolve and forces them to confront the true nature of their enemy.