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The city of Antioch-on-the-Orontes (modern Antakya) is located in modern-day Turkey. It was founded near the end of the 4th century BC by Seleucus I Nicator, who made it the capital of his empire in Syria. Seleucus I had served as one of Alexander the Great's generals, and the name Antiochus occurred frequently amongst members of his family.

Antioch occupies an important place in the history of Christianity. It was here that Paul preached his first Christian sermon in a synagogue, and here that followers of Jesus Christ were first called Christians (Acts 11:26). As Christianity spread, Antioch became the seat of one of the four original patriarchates, along with Jerusalem, Alexandria, and Rome. Today it remains the seat of a patriarchate of the Roman Catholic and Oriental Orthodox churches. One of the canonical Eastern Orthodox churches is still called the Antiochian Orthodox Church although it moved its headquarters from Antioch to Damascus, Syria, several centuries ago.

For several centuries Antioch was an important city in the Roman Empire. The emperor Aurelian erected several magnificent public structures, and later the emperor Constantius II erected an octogonal cathedral, which suffered in the earthquake of AD 526. The Persians captured the city in 540. The Byzantines recovered Antioch, only to have the Muslims conquer it in 636.

The city remained in Arab hands until 969, when it was recovered by the Byzantine Emperor Nicephorus II Phocas. The city was lost again, to the Seljuk Turks, in 1085. 13 years later, it was captured by the Crusaders, and became the capital of an independent Principality of Antioch. The city remained in Crusader hands for the better part of the 12th and 13th centuries, until it was finally captured by the Mamluk Sultan Baibars in 1268. Baibars destruction of the city was so great that it was never a major city again, with much of its former role falling to the port city of Alexandretta (Iskenderun).

Antakya is the capital of the province Hatay.

Several other cities within the Seleucid empire were also named Antioch, most of them founded by Seleucus I Nicator.

Antioch is also the name of a number of places in the United States of America: see and in Canada:
Antioch is also a famous university (formerly a college) in Yellow Springs, Ohio; the second institution to provide coeducation at the college level in the United States. See Antioch College.