It is located in the most important Coptic center in Egypt, known as Anba Ruwais. The cathedral is the only church in Egypt that was built by an Egyptian government despite the long history of Christianity in Egypt. On 24 July 1965 President Gamal Abd al-Nasser laid its foundation stone. On 26 July 1968 Patriarch Cyril VI (1959-1971) and the Ethiopian Emperor Selassie I inaugurated the cathedral on the occasion of the transfer of the relics of St. Mark the Evangelist from to Cairo.

The papacy returned the relics to the Coptic Church as a gesture of goodwill between the two churches. The cathedral is one of the largest churches in Africa. Its imposing structure measures 100 meters long, 36 meters wide, and 55 meters high. The belfry is 85 meters high. There are two shrines on the ground floor under the cathedral. One houses the relics of St. Mark and the other the relics of St. Athanasius (326-373); on 6 May 1973 Pope Shenouda III received the relics from Paul VI in Rome.

The papal residence lies in front of St. Mark’s Cathedral. This Coptic compound includes the medieval church of St. Ruwais, the Clerical College, the Higher , the new cultural center with the library, and other Coptic institutions.