The Museum of Byzantine Culture aims in presenting various aspects of life during the byzantine and post-byzantine periods: art, ideology, social structure and religion, as well as how historical changes and the political situation were affecting people' s everyday life.

At the same time, the activity of the Department of Educational Programmes, the good structure and function of the conservation laboratories and of the archaeological material storerooms, the provision of scientific know-how to other Balkan countries, the organisation of scientific meetings and conferences, as well as the editing and publishing work, render the Museum into an exceptionally important centre for the preservation, research and promotion of Byzantine and Postbyzantine culture. Since the Museum' s inauguration in 1994, an annual bulletin is published, the first of its kind by a Greek public museum. 

The Museum of Byzantine Culture was awarded the Council of Europe Museum Prize for 2005, following the concurrent recommendation of the Council' s Committee for Culture, Science and Education.

The founding of the Museum of Byzantine Culture and its official opening in 1994 in Thessaloniki, the most "Byzantine" city of the modern Greek state, marks the end of a story that had begun long before, just after the city' s liberation in 1912.

In August 1913, a decree issued by the Governor General of Macedonia, Stephanos Dragoumis, resolved to establish a "Central Byzantine Museum" in Thessaloniki. At the suggestion of the Metropolitan of Thessaloniki, Gennadios, it was decided that it would be housed in Acheiropoietos Church. The decision was never carried out, however. Instead of Acheiropoietos, a government decree issued in 1917 appointed the Rotunda as the new Macedonian museum, and large numbers of Christian sculptures were collected there, some of them remaining on display in the Rotunda until the earthquake of 1978. Meanwhile, the Christian and Byzantine Museum was founded in Athens in 1914, and in 1916 antiquities were transferred en masse from Thessaloniki to Athens "for their own protection" and eventually included in the collection of the Byzantine Museum in Athens.

The question of founding the Museum resurfaced in actuality after the change of polity in 1975. In 1977 a nationwide architectural competition was announced and it was won by the entry submitted by Kyriakos Krokos.

The foundation stone was laid in March 1989 and the building was completed and handed over in October 1993. The antiquities that had been transferred to Athens in 1916 returned in June 1994, part of which was displayed in the museum' s inaugural exhibition, "Byzantine Treasures of Thessaloniki: The Return Journey", which opened, together with the museum, on 11 September 1994.

The 11 rooms that comprise the Museum' s permanent exhibition opened gradually to the public from 1997 to early 2004.

Since 1997 the Museum of Byzantine Culture has had the status of an independent regional unit of the Ministry of Culture with its own director.