Archbishop Paisi brought about close ties between the Albanian Orthodox Church and the Moscow Patriarchate. These ties were further strengthened after a delegation of Soviet religious leaders, headed by Bishop Nikon of Odessa, visited Tirana in the spring of 1951. After the 1960-61 Moscow-Tirana break, however, these ties lapsed.

The Roman Catholic Church, chiefly because it maintained close relations with the Vatican and was more organized than were the Muslim and Eastern Orthodox faiths, became a principal target of persecution as soon as the Communists assumed power. In May 1945 Monsignor Nigris, the apostolic nuncio in Albania, was arrested on charges of fomenting anti-Communist feelings and deported to Italy. In 1946 a number of Catholic clergymen were arrested and tried on charges of distributing leaflets against the regime; some were executed, others given long prison terms at hard labor.

According to Vatican sources, from 1945 to 1953 the number of Catholic churches and chapels in Albania was reduced from 253 to 100. Both seminaries in the country were closed, and the number of monasteries dropped from ten to two. All twenty convents were closed, as were fifteen orphanages, sixteen church schools, and ten charitable institutions. Both Catholic printing presses were confiscated, and the publication of seven religious periodicals ceased.

The ranks of Catholic priests were thinned from ninety-three in 1945 to ten in 1953, twenty-four having been executed, thirty-five imprisoned, ten either missing or dead, eleven drafted into the army, and three having escaped from the country. Secular officials and laymen active in church affairs also suffered execution, imprisonment, and harassment.

The Catholic school system was completely eliminated. This included five secondary schools with a total enrollment of 570 and ten elementary and vocational schools with 2,750 pupils. All Catholic associations were suppressed.

A severe blow against the Catholic church was struck in 1951, when the regime mustered a small group of clergymen to hold a national Catholic assembly to draw the statute for the church. As approved by the Council of Ministers on July 30 of that year, the statute provided that the "Catholic Church of Albania has a national character ... [and that] it shall no longer have any organizational, political, or economic relations with the Pope." The statute provided further that the church was to be directed both in religious and administrative matters by a new Catholic Episcopate, that relations concerning religious questions could be established only through governmental channels, and that the church would submit to the canon law of the world Catholic church only if the provisions of this law did not contradict the laws of the People's Republic of Albania.

Enver Hoxha himself spearheaded the campaign against the Catholic church. In 1952, for example, he purged Tuk Jakova, the only Catholic member of the Politburo and previously one of Hoxha's closest collaborators, because he had allegedly befriended the Catholic clergy. In his speech to the Second Party Congress in 1952, in an attempt to justify Jakova's purge, Hoxha said: "Comrade Tuk Jakova, in contradiction to the political line of the Party and of the state concerning religion generally and the Catholic clergy in particular, has not properly understood and has not properly acted against the Catholic clergy. Without seeing the great danger of the reactionary clergy, Comrade Tuk Jakova has not hated them in sufficient measure...."

A new policy aimed at the complete destruction of organized religion was enunciated by Hoxha in a speech to the Party's Central Committee on February 6, 1967. Calling for an intensified cultural-education struggle against religious beliefs and declaring that the only religion for an Albanian should be Albanianism, he assigned the antireligious mission to the youth movement. By May of the same year religious institutions were forced to relinquish 2,169 churches, mosques, cloisters, and shrines, most of which were converted into cultural centers for young people. As the literary monthly Nendori (November) in its September 1967 issue reported the event, the youth had thus "created the first atheist nation in the world."

According to Western correspondents in Tirana, the procedure employed in seizing the places of worship was to assemble the villagers or parishioners in order to discuss Hoxha's speech and to take measures to eliminate what the regime referred to as harmful survivals of religious customs. A decision was then taken to ask the government for permission to close a church, mosque, or monastery. A few days later the government, stating that it was following the will of the people, would issue orders to close the house of worship.

Drastic measures were reportedly taken in cases where the clergy opposed the government order. The strongest resistance came from the Catholic clergy, resulting in the detention of some twenty priests. The cloister of the Franciscan order in Shkoder was set afire in the spring of 1967, resulting in the death of four monks. The Catholic cathedral in Tirana had its facade removed, and on June 4, 1967, it was taken over by the government and converted into a museum. A similar fate befell the Catholic cathedrals in Shkoder and Durres.