After the fall of the kingdom of Macedon in 146 BC, Thessaloniki became part of the Roman Empire. It became an important trading center on the Via Egnatia, a Roman road that connected modern Istanbul with modern Ancient Thessaloniki had a sizeable Jewish colony and was an early center of Christianity. On his second missionary journey, the Apostle Paul preached in the city's synagogue, the chief synagogue of the Jews in that part of Macedonia, and laid the foundations of a church. Opposition against him from the Jews drove him from the city, and he fled to Veria.
By the time Constantine converted to Christianity in the 4th century, Thessaloniki's importance was second only to Constantinople itself in the Eastern Roman Empire. Shortly before the Empire was Christianized, in 306 AD, Thessaloniki acquired a patron saint, St. Demetrius. He was the Roman proconsul of Greece under the anti-Christian emperor Maximian and was martyred. His relics are still housed and venerated in Thessaloniki at the St. Demetrius Church.
Emperor Theodosius I was the one who made Christianity the official religion of the Roman Empire in 381 AD. He also, in 390 AD, massacred 7,000 to 15,000 of the citizens in the city's hippodrome in revenge for a revolt. The act earned Theodosius a temporary excommunication.
After the fall of the Roman Empire in 476 AD, repeated barbarian invasions left Macedonia depopulated. In the 7th century, the Slavs failed to capture Thessaloniki but a sizeable Slavic community nonetheless established itself there. This led to St. Cyril and his brother St. Methodius, who were born in Thessaloníki and spoke Slavonic, being encouraged by the Byzantine Emperor Michael III to visit the northern Slavic regions as missionaries. Their adopted South Slavonic speech became the basis for the Old Church Slavonic language.
Thessaloniki was occupied by the Saracens in 904 and by the Norman rulers of Sicily in 1185, with considerable destruction and loss of life on both occasions. It finally passed out of Byzantine hands for good in 1204, when Constantinople was captured by the Fourth Crusade in 1204. Thessaloníki and its surrounding territory — the Kingdom of Thessalonica — became the largest fief of the Latin Empire, covering most of north and central Greece. The city was recovered by the Byzantine Empire in 1246, but, unable to hold it against the encroachments of the Ottoman Empire, the Byzantine Despot Andronikos Palaeologus was forced to sell it to Venice, who held it until it was captured by the Ottoman ruler Murad II in 1430. 
Thessaloniki, renamed Selânik, remained in Ottoman hands until 1912 and became one of the most important cities in the Empire, with a large port being built in 1901. The founder of modern Turkey, Kemal Atatürk, was born in Thessaloniki in 1881. The city was extremely multicultural: of its 130,000 inhabitants at the start of the century, around 60,000 were Sephardic Jews, whose ancestors had fled Spain and Portugal after 1492; the city's language of daily life was Ladino, a Jewish language derived from Spanish; and the city's day off was Saturday, the Jewish Sabbath. Turks, Greeks, Bulgarians and Albanians made up the remainder of the population.
Thessaloniki was the main prize of the First Balkan War of 1912, during which it was successfully captured by Greece (October 1912). King George I of Greece was assassinated in Thessaloniki in March 1913. In 1915, during World War I, a large Allied expeditionary force landed at Thessaloniki to use the city as the base for an offensive against pro-German Bulgaria. A pro-Allied temporary government headed by Eleftherios Venizelos was established there, against the will of the pro-neutral German King of Greece.
Much of Thessaloniki was devastated by a fire in 1917 of unknown origin, probably an accident. Venizelos forbade the reconstruction of the town center until a full modern city plan was prepared. This was accomplished a few years later by the French architect and archeologist Ernest Hebrard. The Hebrard plan swept away the Oriental features of Thessaloniki and transformed it to a European-style city.
One consequence of the fire was that half the city's Jewish population left for places like Palestine, Paris, or America. But their numbers were quickly replaced by refugees after huge numbers of ethnic Greeks were expelled from Turkey in 1922 following the Greco-Turkish War. The city expanded enormously as a result. It was nicknamed "The Refugee Capital" (I Protévoussa ton Prosfígon) and "Mother of the Poor" (Ftohomána), and even today the city's inhabitants and culture are distinctively Anatolian in character.
Thessaloniki fell to the forces of Nazi Germany in 1941 and remained under German occupation until 1944. The city suffered considerable damage from Allied bombing, and almost the entire Jewish population was exterminated by the Nazis. Barely a thousand Jews survived. However, Thessaloniki was rebuilt fairly quickly after the war.
