After the conquest of Istanbul, the church's location close to the barracks of the Janissaries saw it transformed into a de facto 'inner arsenal' for storing their weapons (Turkish: İç Cebehane).

By 1726, during the reign of Sultan Ahmed III, it functioned as a full-fledged armory known as Dar-ül Esliha (Turkish: House of Weapons).

[citation needed] Appointed to the role in 1881, the first curator and founder of the museum was Osman Hamdi Bey, Painter, Archeologist and son of İbrahim Edhem Pasha, an Ottoman Grand Vizier.

Modern conservation experts refer to this as the first 'protection law' issued by the Ottoman State, focusing on permissions to carry out excavations and related artifact management.

[8] With this imperial decree for protecting cultural goods now being enforced, provincial governors throughout the Ottoman Empire would send in found artefacts to the capital city, thus further growing the collection.

[citation needed] With subsequent major finds being discovered shortly thereafter, e.g. excavation of the necropolis of King Sidon in modern-day Lebanon, it soon became clear that a purpose-built building large enough to house the growing museum collection was required.

Collections are relating to Anatolian history, including the Early Bronze Age, Assyrian Colony Period, Hittite, Neo-Hittite, Urartian, Aramean, as well as Mesopotamian, Egyptian, Syrian, Iran, Palestinian and Ancient Arabian cultures.

[citation needed] The museum has a large collection of Turkish, Hellenistic and Roman artifacts, many gathered from the vast former territories of the Ottoman Empire.