A church dedicated to St. Demetrius, the patron saint of Thessaloniki, existed on this site during the Ottoman era and was the cathedral of the city.

During the Greek Revolution of 1821, hundreds of Thessalonians sought refuge in the church, but the Ottomans broke down the doors and massacred them.

[1] The miraculous icon of Saint Demetrius, the Patriarchal Throne, and many documents of the Greek community are kept in the church.

In October 1890, Metropolitan Sophronios [bg] (1889–1893) applied for a permit to build a new church, which was issued in early June 1891.

[5] Work halted in 1892 because the municipality accused the design contractors of using poor-quality materials, and of deviating from Ziller's original plan.

[6] The church was inaugurated when the city was already part of Greece, on 21 April 1914 by Metropolitan Gennadios [el] (1912–1951).

It has neoclassical, neo-Romanesque, and neo-Renaissance characteristics, and thus follows the eclectic trend characterizing Thessaloniki architecture at the end of the 19th century.

The nave is in the form of an inscribed equilateral cross and is covered by a large dome,[1][6] and there are four tall bell towers on four sides of the building.