After the expulsion of Eudoxius from the see of Antioch, the Arians of Antioch, believing that Meletius of Armenia would uphold their doctrines, petitioned the Emperor Constantius to appoint Meletius Bishop of Antioch, while signing a document jointly with the Orthodox of Antioch, unanimously agreeing to Meletius' appointment (see Feb. 12); this document was entrusted to Eusebius, Bishop of Samosata. Meletius, however, after his Orthodoxy became apparent, was banished, and the Arians persuaded Constantius to demand the document back from Eusebius, as it convicted their perfidy. Imperial officers were sent; Eusebius refused to surrender the document without the consent of all who had signed it; the officers returned to the Emperor, who furiously sent them back to Eusebius with threats. But so great a zealot for the true Faith, so staunch an enemy of the Arians, so fearless a man of valor was Saint Eusebius, that when Constantius' officers arrived, threatening to cut off his right hand unless he surrendered the document, Eusebius held out both hands. When Constantius learned of it, he was struck with astonishment and admiration.

This took place in 361, the last year of the reign of Constantius; he was succeeded by Julian the Apostate, who was slain in Persia in 363; Jovian succeeded Julian, and Valentinian succeeded Jovian in 364, making his brother Valens Emperor of the East. Valens, who supported the Arians, exiled Eusebius to Thrace in 374. The bearer of the edict of Eusebius' banishment arrived in the evening; Eusebius bade him keep silence, or else the people, learning why he had come, would drown him: and Eusebius, though an old man, left his house alone on foot by night. After Valens was slain at Adrianopole in 378 (see Saint Isaacius, Aug. 3), the holy Eusebius returned from exile under the Emperor Gratian, and he ordained for the churches of Syria men known for their virtue and Orthodoxy. About the year 380, as he was entering a certain village to enthrone its bishop, whom he had consecrated, an Arian woman threw a clay tile from the roof, and it crushed his head; as he was dying, he bound the bystanders with oaths that they not take the least vengeance. Saint Gregory the Theologian addressed several letters to him (PG 37:87, 91, 126-130); he had such reverence for him, that in one letter to him, commending himself to Saint Eusebius' prayers, he said, "That such a man should deign to be my patron also in his prayers will gain for me, I am persuaded, as much strength as I should have gained through one of the holy martyrs.