名门高中椚椚丘中学的垫底班级3年E班，在新一学年迎来了一个奇怪的老师（二宫和也 配音）。这个老师长着圆圆的黄色大脑袋以及黏滑恶心的触角，原来他就是不久前将月亮炸成月牙的罪魁祸首。日本防务省特种部队的精英乌间惟臣（椎名桔平 饰）向学生们介绍了怪物的情况，他拥有20马赫的超快速度，人类寻常的武器对他完全不起作用。为了阻止怪物一年后摧毁地球的阴谋，人类必须想方设法除掉他。而怪物自告奋勇愿意出任3年E班的班主任，于是乎手无缚鸡之力的学生们担当起刺杀怪物的重任。此后，学生们接受了乌间的严格培训，而杀手比琪（知英 饰）、智能机器人自律思考固定炮台（桥本环奈 饰）、转学生堀部系成（加藤清史郎 饰）以及教官鹰冈明（高岛政伸 饰）等强大对手也相继来到这间暗杀教室内，搞怪的“杀老师”将面临永无止息的刺杀行动…… 本片根据松井优征的超人气漫画改编。
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