He attended the Russian Orthodox Tiflis Seminary and then the Pontifical Urban University in Rome in 1906. His outstanding performance in the latter was noted by Pope Pius X, who told young Agagianian: "You will be a priest, a bishop, and a patriarch." He was ordained priest in Rome on December 23, 1917. Despite the upheaval bought by the Russian Revolution, he thereafter served as a parish priest in Tiflis and then as the head of the city's Armenian Catholic community from 1919. He left for Rome in 1921 when Georgia was invaded by the Red Army and did not see his family until 1962, when his sister Elizaveta traveled to Rome through the intervention of Soviet leader Nikita Khrushchev.