During the 12th century, the Byzantine Empress Irene and Emperor John II Kommenos commissioned the Pantocrator, a three-church monastic complex, to serve as the dynastic mausoleum for themselves and later Byzantine emperors. In the 14th and 15th centuries, Palaeiologan emperors were also buried in the multi-domed structure in the heart of what is now the old city of Istanbul.

After the Ottoman conquest in 1453, the buildings were converted to a Medresse (Koranic school) and subsequently to a mosque. One part of the Zeyrek Camii is still used for Muslim worship. But the building is situated in a poor neighborhood of immigrants who have little historical and cultural attachment to it. The impressive structure has been allowed to deteriorate in the past. Because the structure remains relatively stable, the most immediate actions required are to secure it from further damage from the weather. Restoration work is on its way but funding is still needed to complete re-roofing, replace all the windows, repair damaged walls, and consolidate interior surfaces.

Zeyrek Mosque is selected as 100 most endangered sites of the world by World Monuments Fund.