After his ordination in 1928, Hopko was assigned to Prague, the capital city of Czechoslovakia. By 1930 there were over 12,000 faithful registered with the parish, a mix of Ukrainians, Rusyns and Slovaks. He strove to deepen their faith and emphasized the need for the different ethnic groups to cooperate to have a flourishing parish and build up the Body of Christ. Hopko’s relations with the local Latin Church helped secure the gift of the church of Saint Clement in 1931 from the Archdiocese of Prague, and a second Greek Catholic parish was founded in Brno. Unfortunately, ethnic tensions resulted in most of the Ukrainians boycotting the services until a Ukrainian priest came. Hopko himself established as his motto for the parish "I did not come for Russians, nor for Ukrainians, nor for Ruthenians, but for Greek Catholics".
In 1938 the Munich Crisis resulted in the collapse of Czechoslovakia, becoming a quasi-independent republic and an ally of the Third Reich. Slovakia eventually betrayed most of its Jews by sending them to death camps, and the new regime persecuted non-Slovak minorities. The state ordered the removal of Hopko from his positions as Spiritual Director of the seminary because he was Rusyn.
In 1945 Czechoslovakia was occupied by the Red Army, and the Communist Party was given great influence. That included steadily worsening conditions for the Catholic Churches, and growing support for the Russian Orthodox Church. Gojdich applied to the Holy See to have an auxiliary bishop appointed in 1947. Pope Pius XII chose Hopko. His episcopal motto “That all may be one” was aimed at healing the ethnic divisions in the eparchy along with the hope of the return of Orthodoxy and Catholicism, but his consecration as bishop was opposed by some of the Slovak clergy. He and Gojdich agreed to focus their efforts on the religious education of the young and apologetics against atheism, and they poured their energy into publications and pastoral visits around the country.
An attempt to bring about “socialism with a human face” launched a rapid de-Stalinization of the country. There were high hopes for liberalization and freedom for political prisoners, including restoration of the Greek Catholic Church. Through the help of some of Hopko’s former students, the Communist Party asked for the formal recognition of the Greek Catholic Church.