The church of Agios Dimitrios is a Byzantine five-aisled basilica, that was built in the first half of the 7th century AD. It is the third and the largest temple that was erected on the same site, following an earlier Paleochristian three-aisled basilica of the 5th century that was destroyed by fire, and a small oratory of the 4th century. Many of the architectural elements and mosaics of the previous basilica were incorporated into the final church. Earlier on the site, there was a Roman bath where, according to Christian tradition and hagiology, Demetrius of Thessaloniki became a martyr during the Diocletian Persecution (some scholars are identifying him with Demetrius of Sirmium). For centuries, Thessaloniki and the church of Agios Dimitrios were the centers of his worship and every October the Dimitria religious festival was taking place in his honor. The festival was revived in 1962 and it still takes place in the form of several cultural events throughout the entire month. For the Christians of Thessaloniki, Saint Demetrius was and still is the patron Saint and protector of the city (he is officially celebrated on October 26).

Following the Ottoman conquest of Thessaloniki, and like most of the city’s Byzantine churches, the basilica of Agios Dimitrios was converted into a mosque at the end of the 15th century. It was restored back into a Christian church after the Greeks took back the city from the Ottomans on October 26, 1912 (on the feast day of Saint Demetrius). In the Great Fire of Thessaloniki, in 1917, the monument was severely damaged. The wooden roof, the upper walls, the galleries and many of its mosaics and wall-paintings, were destroyed. The restoration process lasted for decades and the church did not function again until 1949. The crypt and the ruins of the Roman bath on which the church was built, were discovered during the archaeological excavations that were held at that time (during the Ottoman Period the crypt was filled with earth). Inside the crypt, there is a fountain that was used as a source of holy water and a small church left of the entrance (the latter is assumed that it is the 4th-century oratory which was built at the same place where Saint Demetrius was killed). Today, the crypt hosts a permanent exhibition with findings that were discovered on site. It is accessed by stairs that are located inside the church, close to the south column of the chancel.

The mosaics that survived through the fire of 1917 are dated between the 5th and the 9th century and are considered fine examples of Paleochristian and Byzantine Art. They are located on the two columns, left and right of the chancel, and on the walls above the left and the right openings between the narthex and the nave. Only a few wall-paintings have been saved, mostly at the south aisle and the narthex. The beautiful ornate marble capitals of the columns (at the aisles, the galleries, the narthex tribelon, and the windows) probably belonged to the earlier three-aisled basilica, or to other, even older, Roman or Christian buildings. They were reused in the 7th-century basilica and again during its restoration following the fire of 1917.

At the west of the outer north aisle, there is a remaining part of the old Roman bath that has been incorporated into the temple as an internal chapel containing the cenotaph of Saint Demetrius. This was the only place where the Christians could worship their Saint after the church was converted into a mosque. In the south-east corner of the temple, there is also the chapel of Saint Euthymius that was built in the 13th century. The latter contains wall-paintings of the early 14th century, that belong to the art of the Paleologan Period. In the midst of the outer north aisle of the basilica, there are the relics of Saint Demetrius, kept inside a marble ciborium. Every day, hundreds of pilgrims visit the church just to worship the relics of their Saint.