The 77th group of students at Hope's Peak Academy begin their studies with Chisa Yukizome as their homeroom teacher. Meanwhile, Hajime Hinata, a student without any outstanding talent in the Reserve Course, participates in an experiment to become the Ultimate Hope. However, a series of disastrous events triggers the emergence of the Remnants of Despair and the "Biggest, Most Awful, Most Tragic Event in Human History." This storyline occurs simultaneously with Danganronpa 3: Mirai-hen, which aired before this installment.