Born on the village of Agios Theodoros in the island of Imvros, Ottoman Empire on July 29, 1911, to Maria and Athanasios Koukouzis, he had two sisters Virginia and Chrysanthi and a brother Panagiotis.

Five years after his ordination, Deacon Iakovos received an invitation to serve as Archdeacon to the late Archbishop Athenagoras, the Primate of North and South America, who later (1949–72) became Ecumenical Patriarch of Constantinople.

On February 14, 1959, the Holy Synod of the Ecumenical Patriarchate elected Iakovos as successor to Archbishop Michael, who died July 15, 1958, as primate of the Greek Orthodox Archdiocese of America.

[2] In addition to his duties as primate, Archbishop Iakovos was Exarch of the Ecumenical Patriarchate of Constantinople; president of the board of education of the Greek Orthodox Archdiocese of North and South America; founder and chairman of the Standing Conference of the Canonical Orthodox Bishops in the Americas (SCOBA); chairman of the Orthodox-Roman Catholic Consultation in the U.S., and of the Bishops' Committee for Ecumenical and Interreligious Affairs; honorary board of the Advisory Council on Religious Rights in Eastern Europe and the Soviet Union, and of the United States Senate Committee on Foreign Relations.

Iakovos, who had experienced religious oppression himself as a child, accepted Dr. King's invitation demonstrating his commitment to freedom and civil rights as key principles of the American life.

[7] Iakovos came into conflict with the Ecumenical Patriarch Bartholomew I after he supported a move by 29 bishops towards the administrative unification of Eastern Orthodox churches in America at the Ligonier Meeting.