After he defended his doctoral thesis in 1955, he received the degree of “vartabed” (doctor of the Church). He was a faculty member and then served as dean of the seminary. He studied theology for two years at Oxford University. In 1963 he became an aide to Catholicos Khoren I. The same year he was elevated to senior archimandrite and in 1964, consecrated bishop.
In the 1970s, he served in important administrative positions. From 1971-1973 he was Prelate of the Diocese of New Julfa (Iran) and in 1973 he received the rank of archbishop. He was appointed Pontifical Legate of the Eastern Prelacy from 1973-1975 and Prelate from 1975-1977. He left his position in 1977 when he was elected Catholicos Coadjutor of the Catholicate of Cilicia. He served in this position until the death of Catholicos Khoren in 1983, when he became Catholicos Karekin II of the Holy See of Cilicia.
His ecclesiastical, administrative, and intellectual activities, including his ecumenical contacts and his frequent and valuable publications in Armenian, English, and French on theological, Armenological, philosophical, ethical and other subjects, had already earned him a position of importance in the hierarchy of the Armenian Church. He bolstered his activities during his twelve-year tenure as Catholicos (1983-1995). He developed a close relationship with Catholicos of All Armenians, Vazken I (1955-1994).
Upon the death of Catholicos Vazken, Catholicos Karekin II was elected Catholicos of All Armenians in April 1995 and thereafter became known as Karekin I. These were the first years of the second independence of Armenia. The newly elected Catholicos was called to have a central role in the resurgence of the Armenian Church after the collapse of the Soviet Union. However, his health failed him and his pontificate was extremely brief. After a painful battle with cancer, he passed away on June 29, 1999.