He quickly became a favorite of King Peroz I, who preferred his compliant stance to that of Babowai, Catholicos of Seleucia-Ctesiphon and head of the Persian Church, whom he regarded as a pro-Roman traitor.
Over time Barsauma and Babowai's relationship grew openly antagonistic and came into conflict over the issue of the marriage of bishops, which provoked outrage in the Church of the East.
In 485 Barsauma's political enemies consecrated as patriarch the moderate churchman Acacius of Seleucia-Ctesiphon in the hope that he would prevent the takeover of the Church of the East by the Nestorians.
The following year the proposed council was held in Ctesiphon, however Barsauma did not participate, and the synod agreed to endorse the teachings of Theodore of Mopsuetia as official doctrine and the marriage of all clergymen.
Barsauma died in 491, according to Bar Hebraeus he was killed by monks from Tur Abdin with the keys of their cells, however he also mentions how his tomb may be found in the Church of Mar Jacob in Nisibis.