During Byzantine times, it functioned as the katholikon of the Latomos Monastery (Greek: Μονή Λατόμου/Λατόμων), and was adorned with rich mosaic and fresco decoration, which was renewed in the 12th–14th centuries.

Many surviving elements of the Byzantine decoration are of high artistic quality, especially the 5th-century apse mosaic the Icon of Christ of Latomos.

Under Ottoman rule, the building was converted into a mosque (probably in the 16th century), until it was reconsecrated as a Greek Orthodox church in 1921, thus receiving its present name.

The marble decoration in the Church of Hosios David depicted crosses, vines and leaves in swirling detailing.

The east part of the south and north barrel-vaults contains depictions of the nativity, the presentation in the temple, our lady of the passion, Christ on the mount of olives, entry into Jerusalem, theophany, and decorative panels meant to resemble marble slabs.

The frescos: our lady of the passion, the entry into Jerusalem, and Christ on the Mount of Olives are likely later, during the Palaeologan period, approximately c. 1300.