"Koro Teacher Quest!" is a comedic anime series that revolves around the misadventures of Koro-sensei, a peculiar, octopus-like creature with extraordinary abilities. After destroying most of the moon, Koro-sensei becomes a teacher for Class 3-E at Kunugigaoka Junior High School, a group of students relegated to the school's outcast class due to their poor academic performance. Despite his bizarre appearance and destructive potential, Koro-sensei proves to be an exceptionally dedicated and effective teacher, helping his students improve academically and personally.

The central plot involves a high-stakes mission assigned to Class 3-E: assassinate Koro-sensei before he destroys the Earth, as he has threatened to do by the following March. The students are provided with specialized anti-Koro-sensei weapons and training, turning their classroom into a battleground. However, as the students attempt to eliminate their teacher, they gradually uncover his mysterious past and the reasons behind his transformation into a superhuman being. Koro-sensei's backstory reveals his origins as a human assassin subjected to unethical experiments, which transformed him into his current form and granted him immense power.

Throughout the series, the students face various challenges, including rival assassins, government interference, and personal struggles, all while balancing their academic responsibilities. Koro-sensei's unorthodox teaching methods and genuine care for his students foster a unique bond between them, complicating their mission to kill him. The narrative explores themes of redemption, perseverance, and the value of education, blending humor, action, and emotional depth.

Key characters include Nagisa Shiota, a quiet and observant student who becomes one of the most skilled assassins in the class; Karma Akabane, a rebellious and highly intelligent student with a knack for strategy; and Irina Jelavić, a professional assassin posing as an English teacher who initially sees Koro-sensei as a rival but later becomes an ally. The series balances its comedic tone with moments of tension and heartfelt drama, culminating in a poignant conclusion that ties together the students' growth and Koro-sensei's ultimate fate.