Established in its current form in 1454 by the Patriarch, Gennadius Scholarius who appointed the Thessalonian Matthaios Kamariotis as its first director.

The current school building is located near the Church of St. George in the neighborhood of Fener (Phanar in Greek), which is the seat of the Patriarchate.

Designed by the Greek architect Konstantinos Dimadis, the current building was erected between 1881 and 1883 with an eclectic mix of different styles and at a cost of 17,210 Ottoman gold pounds, a huge sum for that period.

The money was given by Georgios Zariphis, a prominent Greek banker and financier belonging to the Rum community of Istanbul.

[1] Despite its function as a school, the building is often referred to as "the 5th largest castle in Europe" because of its castle-like shape.