Jacob was appointed bishop, in 308, of the Christian community of Nisibis in Mesopotamia (modern Nusaybin, located near the Turkey/Syria border). Jacob of Nisibis, also known as James of Nisibis and as Jacob of Nusaybin, is recorded as a signatory at the First Council of Nicaea in 325. He was the first Christian to search for the Ark of Noah, which he claimed to find a piece of on a mountain, Cudi Dagi, in a region near Ararat, 70 miles from Nisibis.
He founded the basilica and theological School of Nisibis after the model of the school of Diodorus of Tarsus in Antioch. It was not until the 10th century that the "Persian Sage" identified with Jacob of Nisibis was finally identified with Aphrahat. He was the teacher and spiritual director of Saint Ephrem the Syrian, a great ascetic, teacher and hymn writer who combatted Arianism.
Saint Jacob of Nisibis's relics are in Edessa. He is commemorated in the Coptic Synaxarion on the 18th day of Month of Tobi (usually 26 January). In the Roman Catholic Church he is commemorated on 15 July.