Aidoo's works of fiction particularly deal with the tension between Western and African world views. Her first novel, Our Sister Killjoy, was published in 1977 and remains one of her most popular works. Many of Aidoo's protagonists are women who defy the stereotypical women's roles of their time,like in "Anowa". Her novel Changes won the 1992 Commonwealth Writers' Prize for Best Book (Africa). She is also an accomplished poet - her collection Someone Talking to Sometime won the Nelson Mandela Prize for Poetry in 1987 - and has written several children's books.
In 2000 she founded the Mbaasem Foundation, a non-governmental organization based in Ghana with a mission "To support the development and sustainability of African women writers and their artistic output".
Aidoo is the editor of the 2006 anthology African Love Stories.