In a bizarre twist of fate, Kunugigaoka Junior High School's Class 3-E finds themselves tasked with an impossible mission: assassinate their new homeroom teacher, a powerful, tentacled being who has destroyed seventy percent of the moon and threatens to do the same to Earth within a year. This enigmatic creature, dubbed Koro-sensei, possesses incredible speed, strength, and intelligence, making him seemingly invincible. Yet, he surprisingly dedicates himself to teaching his students, not only academic subjects but also essential life skills and assassination techniques.

The students, initially filled with fear and confusion, gradually develop a complex relationship with Koro-sensei, learning valuable lessons about teamwork, self-improvement, and the importance of seizing opportunities. As they hone their assassination skills, they also grapple with their own personal struggles and insecurities, finding guidance and support in their unconventional teacher. The looming deadline of Earth's destruction creates a constant tension, forcing the students to balance their academic pursuits with their assassination training. They must navigate a world of government conspiracies, rival assassins, and their own evolving emotions, all while striving to understand the true motives of their bizarre but beloved teacher.