Theodore Metochites undertook the restoration and renovation of the Kariye Camii around 1315 or 1316, the most important and best documented period of the building. He had been appointed ktetor (founder) of the monastery by the reigning emperor, Andronikos II Palaiologos. Proud to be the first non-imperial founder of an imperial monastery, Metochites' presence is visible throughout the building. His portrait survives above the entrance to the naos, where he is shown offering the church to Christ, and his monograms appear inside and outside. His work was completed by 1321.

Metochites, probably the greatest scholar of his day, was also Minister of the Treasury when he began the project; he was subsequently promoted to Prime Minister. After the emperor, he was the richest and most powerful man in the Byzantine Empire. He was erudite, and extremely rich—the ideal patron. He was undoubtedly personally involved in the reconstruction and decoration of the building.

Istanbul, Kariye Camii, Christ with Theodore Metachites (mosaic)

Metochites' contribution to the rebuilding and renovation of the Kariye Camii was extensive. He rebuilt the naos dome, the cornice which is decorated with his monograms, and he provided for the entire space to be redecorated, including the surviving marble revetments and floors, as well as the partially surviving mosaics. He also enveloped the older building with new additions. The pastophoria (the small chapels adjoining the sanctuary) were rebuilt and decorated with frescoes; a two-storied annex was added to the north side of the naos; two narthexes were added to the west, lavishly decorated with marbles and mosaics; and a funeral chapel or parecclesion was added to the south, decorated with frescoes. At the southwest corner, where the minaret now rises, a belfry was constructed, bearing Metochites' monograms. In his writings, Metochites says that he also provided silver vessels and silk hangings for the church and books for the library.

Metochites explained the main purpose of the decoration of the church as "to relate, in mosaics and painting, how the Lord Himself became a mortal man on our behalf." Accordingly, the elaborate program includes Old Testament ancestors of Christ, Old Testament prefigurations of the Virgin foretelling the miraculous virgin birth, cycles of the lives of the Virgin and Christ, and the Last Judgment.

Metochites ended his days at the Chora and was buried here. Ousted from power in the palace coup of 1328, he was banished to Didymoteicho (Dimitoka) in Thrace, where he spent two miserable years complaining about the local food that gave him indigestion, the wine that went sour, and the meanness of the inhabitants. After many pitiful, if eloquent, letters he was allowed to return to the capital, but to be confined at the Chora monastery. He died there in 1332, a broken man, having first taken monastic vows and assumed the monastic name Theoleptos.