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Mercy Amba Ewudziwa Oduyoye was born on her grandfather's cacao farm in Amoana, near Asamankese, Ghana, in October 1933. She was the first child born to her parents, Charles Kwaw Yamoah and Mercy Yaa Dakwa Yamoah and has eight siblings. Her father was a teacher and pastor who became president of the Methodist Church in Ghana. Her name, Ewudziwa is of Akan origin and was given to her in honor of her grandfather.

She earned a bachelor's degree from the University of Ghana in 1963, a second bachelor's degree from Cambridge University in 1965, and a master's degree from Cambridge in 1969. From 1967 to 1979, she was youth education secretary for the World Council of Churches; from 1987 to 1994, she was Deputy General Secretary for the same organization. She has taught at Harvard University, Union Theological Seminary, and the University of Ibadan. She has also served as president of the World Student Christian Federation and founded the Circle of Concerned African Women Theologians in 1989.

Oduyoye has written four books and more than eighty articles focusing on Christian theology from a feminist and African perspective. In her work she describes herself as both an African feminist and an African women's theologian. She is considered one of the leading Protestant African theologians. One of her central subjects is how African religion and culture influences the experiences of African women. In particular, she has addressed the effects of economic oppression on African women.

Oduyoye has been awarded honorary degrees by University of Amsterdam (1991), Stellenbosch University the University of the Western Cape in 2002 and Yale University in 2008.