Hyakko takes place in the high school division of Kamizono Academy, a fictional gigantic private institution located in Kyushu, Japan, in which the motto is "to bring up talents of students in all departments and fields". Its storyline focuses on the comedic school life of the four main heroines, Torako Kageyama, Ayumi Nonomura, Tatsuki Iizuka, and Suzume Saotome. As the plot progresses, Torako and her friends gradually begin to learn and interact with their classmates in Class 1-6, in which each student has unique and extraordinary personality.