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Ephraim was born in Amida in Mesopotamia. He was born in the later part of the fifth century, but the date of his birth is not known. He served as a military officer during the reigns of Eastern Roman Empire Emperors Anastasius I and Justin I, rising to the position of Count of the East (''Comes Orientis''). Following a severe earthquake in 526, Ephraim was directed by emperor Justin I to oversee the restoration of the city of Antioch. The destruction of Antioch was attributed at the time to the Christians of Antioch falling into the [[heresy|heresies]] of [[Nestorius]] and [[Eutyches]].
During one of his reviews of the reconstruction work. Ephraim came upon a [[bishop]] who had deserted his [[see]] for unknown reasons. Upon meeting Ephraim, the former bishop predicted that he, Ephraim, would be elected to the patriarchal throne of Antioch that had become vacant by the death of Patriarch Euphrasius during the earthquake. Further, he implored Ephraim to not abandon deeds of charity and to struggle firmly against the heretics. The following year Ephraim was elected to the patriarchal throne, the same year, 527, that [[Justinian]] I became emperor.
Ephraim was noted for his virtue, piety, and compassion for all the destitute.