Antioch on the Orontes (; Ancient Greek: , Antikheia h ep Orntou, Learned Koine Greek pronunciation: [anti..ke.a h e.p orn.tu]; also Syrian Antioch) was a Hellenistic, and later, a Biblical Christian city, founded by Seleucus I Nicator in 300 BC. This city served as the capital of the Seleucid Empire from 24063 BC and the Roman province of Syria, and later, Coele Syria. In the Crusades, Antioch served as the capital of the Principality of Antioch, one of four Crusader states that were founded in the Levant. Antioch's ruin lies on the Orontes River, near Antakya, the modern city in Hatay Province of Turkey (Trkiye), to which the ancient city lends its name.

Antioch was founded near the end of the fourth century BC by Seleucus I Nicator, one of Alexander the Great's generals. The city's location offered geographical, military, and economic benefits to its occupants; Antioch was heavily involved in the spice trade and lay within easy reach of the Silk Road and the Royal Road. During the late Hellenistic period and Early Roman period, Antioch's population may have reached a peak of over 500,000 inhabitants (most generally estimate between 200,000250,000), making the city the third largest in the Empire after Rome and Alexandria. The city was the capital of the Seleucid Empire until 63 BCE, when the Romans took control, making it the capital of the province of Syria. From the early fourth century, the city was the seat of the Count of the Orient, head of the regional administration of sixteen provinces. It was also the main center of Hellenistic Judaism at the end of the Second Temple period. Antioch was one of the most important cities in the eastern Mediterranean half of the Roman Empire. It covered almost 450 hectares (1,100 acres) within the walls, of which one quarter was mountain, leaving 300 hectares (750 acres) about one-fifth the area of Rome within the Aurelian Walls.

Antioch was called "the cradle of Christianity" as a result of its longevity and the pivotal role that it played in the emergence of both Hellenistic Judaism and early Christianity. The Christian New Testament asserts that the name "Christian" first emerged in Antioch. It was one of the four cities of Seleucis of Syria, and its residents were known as Antiochenes. 250,000 people may have lived in the city under the early Roman Empire, but it declined to relative insignificance during the Middle Ages due to warfare, repeated earthquakes, and a change in trade routes. The city still lends its name to Greek Orthodox Patriarchate of Antioch, one of the most important churches of the Levant and eastern Mediterranean.

The Byzantine Empire, also referred to as the Eastern Roman Empire or Byzantium, was the continuation of the Roman Empire in its eastern provinces during Late Antiquity and the Middle Ages, when its capital city was Constantinople. It survived the fragmentation and fall of the Western Roman Empire in the 5th century AD and continued to exist for an additional thousand years until the fall of Constantinople to the Ottoman Empire in 1453. During most of its existence, the empire remained the most powerful economic, cultural, and military force in Europe.

The terms "Byzantine Empire" and "Eastern Roman Empire" were coined after the end of the realm; its citizens continued to refer to their empire simply as the Roman Empire (Medieval Greek: Βασιλεία Ῥωμαίων, romanized: Basileía Rhōmaíōn) or Romania (Medieval Greek: Ῥωμανία), and to themselves as Romans (Medieval Greek: Ῥωμαῖοι, romanized: Rhōmaîoi) – a term which Greeks continued to use for themselves into Ottoman times. Although the Roman state continued and its traditions were maintained, modern historians distinguish Byzantium from its earlier incarnation because it was centred on Constantinople, oriented towards Greek rather than Latin culture, and characterised by Eastern Orthodox Christianity.

Several events from the 4th to 6th centuries mark the period of transition during which the Roman Empire's Greek East and Latin West diverged. Constantine I (r. 324–337) reorganised the empire, made Constantinople the new capital and legalised Christianity. Under Theodosius I (r. 379–395), Christianity became the state religion and other religious practices were proscribed. In the reign of Heraclius (r. 610–641), the Empire's military and administration were restructured and Greek was adopted for official use in place of Latin.

The borders of the empire fluctuated through several cycles of decline and recovery. During the reign of Justinian I (r. 527–565), the empire reached its greatest extent after reconquering much of the historically Roman western Mediterranean coast, including Africa, Italy and Rome, which it held for two more centuries. The Byzantine–Sasanian War of 602–628 exhausted the empire's resources, and during the Early Muslim conquests of the 7th century, it lost its richest provinces, Egypt and Syria, to the Rashidun Caliphate. It then lost Africa to the Umayyads in 698. During the Macedonian dynasty (10th–11th centuries), the empire expanded again and experienced the two-century long Macedonian Renaissance, which came to an end with the defeat by Seljuk Turks at the Battle of Manzikert in 1071. Civil wars and the ensuing Seljuk invasion led to the loss of most of Asia Minor. The empire recovered during the Komnenian restoration, and by the 12th century, Constantinople was the largest and wealthiest city in Europe. The empire was delivered a mortal blow during the Fourth Crusade, when Constantinople was sacked in 1204 and the territories that the empire formerly governed were divided into competing Byzantine Greek and Latin realms. Despite the eventual recovery of Constantinople in 1261, the Byzantine Empire remained only one of several small rival states in the area for the final two centuries of its existence. Its remaining territories were progressively annexed by the Ottomans in the Byzantine–Ottoman wars over the 14th and 15th centuries. The fall of Constantinople to the Ottoman Empire in 1453 ended the Byzantine Empire. Refugees fleeing the city after its capture would settle in Italy and other parts of Europe, helping to ignite the Renaissance. The Empire of Trebizond was conquered eight years later in the 1461 siege. The last of the successor states, the Principality of Theodoro, was conquered by the Ottomans in 1475.