Mitsudomoe takes place in the uproarious class 6-3 of an elementary school, where newly hired teacher Satoshi Yabe begins his career as homeroom instructor and immediately loses any hope of an orderly start. The room is packed with eccentric students, but the real source of chaos is the Marui triplets. Mitsuba, the eldest, is sadistic and unusually mature for her age; Futaba is lewd, wildly energetic, and incredibly strong; and Hitoha is quiet, ominous, and often absorbed in erotic books. Each sister has her own way of turning routine school life into a disaster, and Yabe quickly becomes the favorite target of their curiosity.
Once the triplets take an interest in him, they pester Yabe with relentless antics, misunderstandings, and bizarre situations that spiral far beyond ordinary classroom trouble. They rope in the rest of class 6-3, other oddball students, and even the clumsy school nurse Aiko Kuriyama, sometimes abusing Yabe outright and sometimes trying, in their own deeply unorthodox way, to push him closer to her. Everyday rumors, small disputes, and humiliating accidents keep turning simple interactions into escalating slapstick, so Yabe's life at school is anything but boring.