In 1955, he presented his doctoral thesis on the subject "The Theology of the Armenian Church, According to Liturgical Hymns Sharakans" and was promoted to the ecclesiastical degree of vardapet (archimandrite).

He studied theology for two years at Oxford University and wrote The Council of Chalcedon and the Armenian Church, published in 1965 in London.

In 1973, he received the rank of archbishop and was appointed Pontifical Legate of the Eastern Prelacy of the Armenia's Holy Apostolic Church of America (in New York) and in 1975 its Primate.

During his time in the United States, he took special care of the younger generation of Armenians and played a key role in the fundraising for Lebanon in 1976–1977.

When fully installed as Catholicos Karekin II of the Great House of Cilicia, he lavished special attention on religious education, modernizing and promoting the theological seminary.

Karekin wrote several books and booklets in Armenian, English, and French and published many articles and studies on theological, Armenological, philosophical, ethical and literary subjects in periodicals.