It is housed in the city's Ottoman-era bedesten (Μπεζεστένι) a fifteenth-century building in Eleftherias Square.

The Serres bedesten was built by Çandarlı Ibrahim Pasha the Younger around 1493/94.

[1] According to the historian of Ottoman art Semavi Eyice, the Serres bedesten is among the most remarkable specimens of the building type for its excellent construction technique and its striking exterior.

More specifically, there are prehistoric exhibits from the excavations at Promachonas and Kryoneri, Archaic, Classical, Hellenistic and Roman exhibits (mainly ceramics, statues, and inscriptions) from Argilos, Vergi, Terpni, Neos Skopos, Gazoros, ancient Tragilos, and Serres.

Particularly important are the Early Christian and Byzantine exhibits from the town of Serres, most notably a marble icon of Christ and a twelfth-century mosaic of St Andrew the Apostle, both from the Old Cathedral.