She is considered a "founding mother" of modern shōjo manga, especially shōnen-ai. She is also a member of the Year 24 Group.

Moto Hagio made her professional debut in 1969 at the age of 20 with her short story "Lulu to Mimi" in Nakayoshi. Later, for Shogakukan Publishing, she produced a series of short stories for various magazines. Two years after her debut, she published Juichigatsu no Gimunajiumu (The November Gymnasium), a short story which dealt openly with love between two boys at a boarding school. The story was part of a larger movement by female manga artists at the time which pioneered a genre of girls' comics about love between young men. In 1974, Hagio developed this story into the longer Toma no Shinzo (The Heart of Thomas). She was awarded the Shogakukan Manga Award in 1976 for her science fiction classic Juichinin Iru! (They Were Eleven) and her epic tale Poe no Ichizoku (The Poe Family).