Shouya Ishida starts bullying the new girl in class, Shouko Nishimiya, because she is deaf. But as the teasing continues, the rest of the class starts to turn on Shouya for his lack of compassion. When they leave elementary school, Shouko and Shouya do not speak to each other again... until an older, wiser Shouya, tormented by his past behaviour, decides he must see Shouko once more. He wants to atone for his sins, but is it already too late...?

Several ordinary high school students go through their daily routine as two others prepare for something more malevolent.

A class of junior high "misfit" students who are tasked with assassinating their new teacher, an octopus-like creature nicknamed Koro-sensei, who destroyed the moon and threatens to destroy Earth in a year. The students have to learn to balance their assassination attempts with the lessons from Koro-sensei, who is surprisingly an excellent teacher, while the government offers a ¥10 billion reward for his head. Each episode often focuses on individual students, their growth, and their internal conflicts between wanting to kill their teacher and growing to care for him.

安昙小太郎（千叶翔也 配音）出生在一个传统的日本家庭之中，个性细腻而又温厚的他自幼喜欢读书，暗中希望能够成为一名作家，总而言之是班级中并不起眼的存在。水野茜（小原好美 配音）是田径部的种子选手，个性开朗活泼全身上下散发着积极的光芒。这样性格迥异的两人，其生命轨迹被命运推动着联系到了一起。 成熟稳重，可靠正直的比良拓海（田丸笃志 配音）、温柔坦诚，深受朋友们喜爱的西尾千夏（村川梨衣 配音）、严格谨慎，对男生敬而远之的泷泽葵（白石晴香 配音）、古灵精怪，令人捉摸不透的山科浪漫（笔村荣心 配音），在洋溢着青春气息的校园之中，属于他们的乐章正在谱写。