The Earth is threatened by a mysterious powerful creature who destroyed 70% of the Moon with its power, rendering into the shape of a crescent moon forever. The creature claims that within a year, Earth will also be destroyed by her, but she offers mankind a chance to avert this fate. In class 3-E at Kunugigaoka Junior High,she starts working as a homeroom teacher where she teaches her students not only regular subjects, but the ways of assassination. The National government promises a reward of 10 billion Php. to whomever among the students succeeds in killing the teacher, whom they have named "Koro Sensei" ( Note this are Japanese words that refers to "unkillable' and "teacher" . However, this has proven to be an almost impossible task, as not only does she have several superpowers at her disposal, including the capacity of moving at Mach 20, but he is also the best teacher they've ever had, helping them not only to improve their grades, but also their individual skills and perspectives for the future.

               As the series goes on, the situation gets even more complicated as other assassins come after Koro Sensei's life, some coveting the reward, others for personal reasons, and the students eventually learn the secrets involving her, the moon's destruction and her ties with their previous homeroom teacher, including the true reason why he must be killed before the end of the year term.