Mofe-Damijo was born in Warri, Delta State, Nigeria. He attended Midwest College, Warri and Anglican Grammar School and was a member of the Drama Club. He enrolled into the University of Benin to continue his education and studied Theatre Arts. In 1997 Mofe-Damijo returned to the university to study law at the University of Lagos and graduated in 2004.
After graduating from the university, Mofe-Damijo took part in a television soap opera in the late 80's called Ripples. Before then, he had a stint with Concord Newspapers and Metro Magazine as a reporter. Out of Bounds was the first film for which he received a writer/producer credit. In 2005 at the maiden edition of the African Movie Academy Awards Mofe-Damijo won the award for Best Actor in a Leading Role
Mofe-Damijo was the commissioner for Culture and Tourism in Delta State, Nigeria.
Mofe-Damijo was married to the late May Ellen Ezekiel, a foremost Nigerian journalist popularly known as MEE. After MEE's death in 1996, Mofe-Damijo married again, this time to former Jumoke Adegbesan. He has five children in total; four from his current marriage and one from his previous marriage with MEE.