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Thessaloniki was founded as an urban centre by Cassander, a general of Philip II, in 316 BC and named her with the name of the sister of Alexander the Great.
This action was part of the residential policy of Alexander the Great’s successors, aiming at the creation of powerful cities at key locations to ensure communication between the state of Macedon and the rest of the world. An organised port in Thessaloniki was necessary due to the rapid increase in commerce and communication with distant lands.

The administrative organisation of the city during the Hellenistic era followed the model employed in other Greek cities. It retained a type of administrative autonomy after its conquest by the Romans, who contributed to its rapid growth.
The construction of Via Egnatia (146-120BC), connecting Dyrrachium to Evros, helped elevate Thessaloniki to a major commercial, cultural and military centre.
During his tenure as Caesar, Tetrarch Gaius Galerius Valerius Maximianus (250-311 AD) established his seat in Thessaloniki, constructing a magnificent palace, a hippodrome and a triumphal arch (Camara) and turning the city into capital of the Balkans.
The stay of Constantine the Great in Thessaloniki in 322-323 coincides with the implementation of large-scale works in the city, such as the port at its southwestern end. The 4th century was one of great changes for the city, characterised by the pre-eminence of Christianity, at least three centuries after the visit of Paul the Apostle to the city, and marked at its end, in 390, by the massacre of thousands of Thessalonians at the city hippodrome on the orders of Emperor Theodosius I.
By the end of the 5th century, the Roman city had been transformed into a centre of Christianity.

The historical character of Thessaloniki is undoubtedly linked to its Byzantine life.
The walls and extant inscriptions record the tumultuous history of the city. The walled city and its monuments could reasonably be described as an open museum.
From the 7th to the 10th centuries, notwithstanding all the problems that the Byzantine Empire would face with the West, the Arabs, the Slavs, the Bulgarians and the Byzantine Iconoclasm, Thessaloniki continued to develop in all ways, often playing a leading role, thus demonstrating its great importance and position within the structure of the state.
The Christianisation of the Slavs by the Byzantines was an important fact that marked not only that era but the subsequent centuries as well.
The brothers Cyril and Methodius, who were born in Thessaloniki, carried out their missionary work among the Slavs.
The sacking of the city by the Normans in 1185 and its occupation by the Latins for two decades after 1204 briefly suspended but did not stop its cultural growth. Artistic and literary production flourished during the Komnenian period and reached its peak during the Palaeologan era. The turn towards classical Greek education, with the study of ancient texts, highlighted aspects of humanism and led to the Palaeologan Renaissance of literature and art of that period. However, important theological and social controversies had taken place meanwhile, such as the Hesychast strife and the Zealot movement that threw the city into turmoil.
The Byzantine metropolis contains a large number of extant devotional monuments. Each neighbourhood retains its Byzantine or post-Byzantine monument, elements of other times, when the city was the Symvasilevousa (co-reigning city) of a first powerful and then declining Byzantine Empire, or later the centre of an Ottomanoccupied Balkan peninsula. The city was fortunate enough to preserve mainly the monuments of its glorious religious past. The city walls were strengthened either through reconstruction or through new additions, such as the Vardaris fort. The Christian residents of the city, who primarily lived on the plains, built their churches according to the type that was most frequent in the post-Byzantine era: the three-aisled basilica with a low, gabled roof and a portico. After the resettlement of primarily Jewish refugees from Spain in 1500, Thessaloniki acquired a multi-cultural, multi-religious character, which it would retain until its liberation.

Under Ottoman rule (1430-1912), almost all Christian churches, parish or Catholic monasteries were converted into mosques.
The city acquired an Eastern character. Mosques were built throughout its neighbourhoods, new building complexes, religious schools, Bezesteni (an indoor market) and bathhouses became the hubs of the city’s new reality.
The water supply system already in operation with underground and aboveground cisterns was enhanced and expanded. Fountains decorated with ornate sculptures were constructed along the maze-like streets, the Bairia of the Upper/Old City (Ano Poli), to serve the residents and quench the thirst of passers-by.  The city walls were strengthened either through reconstruction or through new additions, such as the Vardaris fort. The Christian residents of the city, who primarily lived on the plains, built their churches according to the type that was most frequent in the post-Byzantine era: the three-aisled basilica with a low, gabled roof and a portico.
After the resettlement of primarily Jewish refugees from Spain in 1500, Thessaloniki acquired a multi-cultural, multi-religious character, which it would retain until its liberation.

The 20th century held a number of changes for Thessaloniki.In 1912, Thessaloniki was liberated and annexed to the Greek state. Within a few decades, major historical events took place in the city.
By the mid-20th century, the city had changed radically in image, size and population. in 1917, a devastating fire reduced the entire centre of the city to ashes.
Thessaloniki was never again the same: 73,000 people were left homeless, entire fortunes, homes and stores were destroyed and the priceless heritage of the 19th century vanished.  The political situation in the Balkans remained as volatile as ever, leading refugees from the surrounding regions and Greeks from the Orient to Thessaloniki. This migration reached its culmination in 1922, with the Treaty of Lausanne and the decision for an exchange of populations leading to an influx of thousands of refugees from Asia Minor. At the same time, the city lost its Muslim population.
Although the damage from the fire had not been restored, refugees settled in churches, in gutted buildings, at unused corners of the city walls, at military camps abandoned by the Allies.
However, above all, new settlements, new neighbourhoods and new suburbs were formed.
Thessaloniki once consisted of 26 ancient towns; the new Thessaloniki now extended across the centuries and throughout new settlements. The former Co-reigning City became the Refugee Capital. in 1941, adding dark pages to the local history.
In 1943, thousands of Thessaloniki Jews were transported by train to Nazi concentration camps and the community of the city was all but annihilated. The subsequent Civil War also had an impact on the city. In 1978, the city suffered a powerful earthquake, leaving in its wake ruins and casualties. During the 1990s, with the dissolution of the Eastern Bloc, numerous economic immigrants arrived in the city.
In 1997, Thessaloniki was the European Capital of Culture.
In 2012, the city celebrated the 100-year anniversary of its liberation and won the title of European Youth Capital for 2014.