When the Roman Empire was divided into eastern and western segments ruled from Byzantium/Constantinople and Rome respectively, Thessaloníki came under the control of the Eastern Roman Empire (Byzantine Empire). Its importance was second only to Constantinople itself. In 390 it was the location of a revolt against the emperor Theodosius I and his Gothic mercenaries. Botheric, their general, together with several of his high officials, were killed in an uprising triggered by the imprisoning of a favorite local charioteer for pederasty with one of Botheric’s slave boys.7,000 – 15,000 of the citizens were massacred in the city’s hippodrome in revenge – an act which earned Theodosius a temporary excommunication.
The quiet era followed until repeated barbarian invasions after the fall of the Roman Empire, while a catastrophic earthquake severely damaged the city in 620 resulting in the destruction of the Roman Forum and several other public buildings. Thessaloníki itself came under attack from Slavs in the seventh century; however, they failed to capture the city. Byzantine brothers Saint Cyril and Saint Methodius were born in Thessaloníki and the Byzantine Emperor Michael III encouraged them to visit the northern regions as missionaries; they adopted the South Slavonic speech as the basis for the Old Church Slavonic language. In the ninth century, the Byzantines decided to move the market for Bulgarian goods from Constantinople to Thessaloníki. Tsar Simeon I of Bulgaria invaded Thrace, defeated a Byzantine army and forced the empire to move the market back to Constantinople. In 904, Saracens based at Crete managed to seize the city and after a ten day depredation, left with much loot and 22,000 slaves, mostly young people.
Despite this, the city quickly recovered, and the gradual recovery of Byzantine power during the tenth, eleventh and twelfth centuries meant that Thessaloniki entered a new golden age of peace and prosperity. The population of the city expanded, and according to Benjamin of Tudela, the city even had a Jewish community some 500 strong by the twelfth century. It also hosted the famous fair of Saint Demetrius every October, which was held just outside the city walls and lasted six days.
The economic expansion of the city continued through the twelfth century as the strong rule of the Komnenoi emperors expanded Byzantine control into Serbia and Hungary, far to the north. The city is known to have housed an imperial mint at this time, another sign of prosperity. However, after the death of the emperor Manuel I Komnenos in 1180, the fortunes of the Byzantine Empire began to decline, and in 1185 the Norman rulers of Sicily, under the leadership of Count Baldwin and Riccardo d’Acerra attacked and occupied the city, resulting in considerable destruction. Nevertheless, their rule lasted less that a year, since they were defeated in two battles later that year by the Byzantine army and forced to evacuate the city.
Thessaloniki passed out of Byzantine hands in 1204, when Constantinople was captured by the Fourth Crusade. Thessaloníki and its surrounding territory—the Kingdom of Thessalonica—became the largest fief of the Latin Empire, covering most of north and central Greece. It was given by the emperor Baldwin I to his rival Boniface of Montferrat but in 1224 it was seized by Theodore Komnenos Doukas, the Greek ruler of Epirus. The city was recovered by the Byzantine Empire in 1246.
At that time, despite the various invasions, Thessaloniki had a large population and flourishing commerce. That resulted in an intellectual and artistic florescence that can be traced in the numerous churches and their frescoes of that era and also by the names of scholars that taught there. (Thomas Magististos, Dimitrios Triklinios, Nikiforos Choumnos, Kostantinos Armenopoulos, Neilos Kavassilas, etc). Many fine examples of Byzantine art survive in the city, particularly the mosaics in some of its historic churches, including the basilica of Hagia Sophia and the church of St George.
In the 14th century though, the city was appalled by the Zelotes social movement (1342-1349). It began as a religious conflict between bishop Gregorios Palamas, who supported conservative ideas and the monk Barlaam, who introduced progressive social ones. Quickly, it turned into a political commotion, leading to the prevalence of the Zelotes, who for a while ruled the city, applying progressive social policies.