He was consecrated Bishop of Berea (Aleppo) in Syria, then of Antioch in 324. He took an active part in the Council of Nicea against the Arian heresy. His zeal for the Faith aroused the hatred of various heretics, who convened a council in Antioch where, by means of slanders and false witnesses, they were able to have the holy bishop deposed and exiled to Thrace, where he died a few years later.

The deposition of the Saint caused a schism in the Church of Antioch which was not healed until 414 (see St Meletius, Feb. 12). Saint John Chrysostom publicly praised Eustathius as a Martyr, and his relics were finally brought back to Antioch in 482. The Synaxarion says "The people then went in jubilation to meet him with lights and incense, and escorted him as he made a triumphal entry into his city, which thus recovered its unity in the Faith and in the veneration of this champion of Orthodoxy."