Cardinal Mafi studied for priesthood at the Pacific Regional Seminary in Suva, Fiji. He was ordained a priest in 1991 at the age of 29. He spent four years in parish work in Ha’apai, Tonga. In 1995 Bishop Foliaki appointed him Vicar-General of the diocese at the age of 34. He spent three years studying religious education at Loyola University, Baltimore, Maryland, graduating in 2000. He was then stationed for six years in Suva (Fiji), engaged in the formation training of local priests. He spent four years in parish work in Ha’apai, Tonga. Cardinal Mafi was appointed consecrated bishop in 2007. When he succeeded Bishop Soane Lilo Foliaki as Bishop of Tonga on 18 April 2008, he became the first diocesan priest to be bishop of the diocese of Tonga.
He participated in the Third Extraordinary General Assembly of the Synod of Bishops on the Pastoral Challenges of the Family in the Context of Evangelization held on October 2014. Cardinal Mafi has been president of the Episcopal Conference of the Pacific since 2010. On 14 February 2015, Pope Francis appointed Cardinal Mafi a cardinal with the title of Cardinal-Priest of Santa Paola Romana. On 13 April 2015, he was appointed a member of the Congregation for the Evangelization of Peoples and of the Pontifical Council Cor Unum for Human and Christian Development.