Sergius was born at Tella, and was a friend of Jacob Baradaeus.^[1] He became a monk at the monastery of Hala, and was ordained a priest by the bishop John of Anazarbus.^[2] As a monk, Sergius accepted the doctrine of tritheism,^[3] and accompanied Jacob Baradaeus to Constantinople in 527.^[4] At Constantinople, Sergius tutored Empress Theodora's grandson Athanasius,^[3] and became a friend of John Philoponus, who wrote a non-Chalcedonian treatise named "A Treatise Concerning the Whole and the Parts" at Sergius' request.^[5]

Jacob Baradaeus, who had become Bishop of Edessa, consecrated Sergius as patriarch of Antioch at Constantinople,^[1][4] thus cementing the schism in the church of Antioch into the non-Chalcedonian Syriac Church and Chalcedonian Greek Orthodox Church of Antioch.^[6] Sources disagree on the date of Sergius' consecration as patriarch.^[7] According to the Zuqnin Chronicle, he was consecrated in 544, whereas John of Ephesus in his Ecclesiastical History dates the consecration to 557.^[7] Sergius resided at Constantinople for the duration of his term as patriarch,^[1] for which he was later erroneously termed patriarch of Constantinople by the 14th-century historian Nikephoros Kallistos Xanthopoulos in his Ecclesiastical History.^[5] He died a natural death,^[1] either in 547 as per the Zuqnin Chronicle, or in 560 as per John of Ephesus.^[7]