Eustathius of Antioch, sometimes surnamed the Great, was a bishop and patriarch of Antioch in the 4th century.

He was a native of Side in Pamphylia. About 320 he was bishop of Beroea, and he became patriarch of Antioch shortly before the Council of Nicaea in 325. In that assembly he distinguished himself zealously against the Arians, though the Allocutio ad Imperatorem with which he has been credited is hardly genuine.

His anti–Arian polemic against Eusebius of Caesarea made him unpopular among his fellow bishops in the East, and a synod convened at Antioch in 330 deposed him for adultery, which was confirmed by the emperor.

For instance, in the dispute with Eustathius of Antioch, who opposed the growing influence of Origen and his practice of an allegorical exegesis of scripture, seeing in his theology the roots of Arianism, Eusebius, an admirer of Origen, was reproached by Eustathius for deviating from the Nicene faith, who was charged in turn with Sabellianism. Eustathius was accused, condemned, and deposed at a synod in Antioch. The people of Antioch rebelled against this action, while the anti-Eustathians proposed Eusebius as the new bishop, but he declined. He was banished to Trajanopolis in Thrace, where he died, probably about 337, though possibly not until 370.

Antioch on the Orontes (Greek: Ἀντιόχεια ἡ ἐπὶ Ὀρόντου; or Ἀντιόχεια ἡ ἐπὶ Δάφνῃ, "Antioch on Daphne"; or Ἀντιόχεια ἡ Μεγάλη, "Antioch the Great"; Syriac: ܐܢܛܝܘܟܝܐ Anṭiokia; Hebrew: אנטיוכיה, antiyokhya; Georgian: ანტიოქია; Armenian: Անտիոք Antiok; Latin: Antiochia ad Orontem; Arabic:انطاکیه, Anṭākiya; also Syrian Antioch) was an ancient city on the eastern side of the Orontes River. It is near the modern city of Antakya, Turkey.

Founded near the end of the 4th century BC by Seleucus I Nicator, one of Alexander the Great's generals, Antioch eventually rivaled Alexandria as the chief city of the Near East and was a cradle of Christianity. It was one of the four cities of the Syrian tetrapolis. Its residents are known as Antiochenes. Once a great metropolis of half a million people, it declined to insignificance during the Middle Ages because of repeated earthquakes, the Crusaders' invasions, and a change in trade routes following the Mongol conquests, which then no longer passed through Antioch from the far east.