Saint James, Bishop of Nisibis, was the son of prince Gefal (Armenia) and received a fine upbringing. From the time of his youth he loved solitude, and for a long time he lived in the mountains around about the city of Niziba located on the border of the Persian and Roman Empires.  Saint James lived as a hermit under the open sky, fed himself with tree fruits and greens, and dressed himself in goat-skins. In summer he lived in the open fields and in the winter in a cave. The monk passed all this time in prayerful conversations with God living a life of strict ascetic discipline.

During a persecution by the Emperor Maximian (284-305) James was glorified by a courageous confession of faith.  On one occasion he went down into the city of Nisibis in Mesopotamia, to look into the faith and life of the Christians. Shortly thereafter, because of his strict and pious life the inhabitants of Nisibis chose him as their bishop around 314 AD. Saint James was glorified by his ardent zeal for the Orthodox Faith, by great miracles and by the gift of clairvoyance. During this period James instructed Saint Ephraim the Syrian in the Christian mysteries.

It happened at one time that the pagan Persian army of Sopor, the emperor of Persia, attacked Nisibis. St James went out onto the ramparts with the banner-icon from the church, himself raising it aloft and walking round the ram-parts fearless of the arrows the enemy was aiming at him. Walking thus, the saint prayed to God to save the city and the faithful in it by sending flies and mosquitoes on the Persians, thus driving them away from the city walls. He did not, we see, seek the destruction of the enemy but some sort of catastrophe, no matter what, even some quite small occurrence, that would overcome them and remove them from the vicinity. God heard the prayer of His chosen one and sent a plague of flies and mosquitoes on the Persians, driving them away and saving the city of Nisibis.

Saint James, among the Fathers of the First Ecumenical Council in 325 AD, was one of the prominent defenders of the Orthodox Faith against the Arians. A wise and educated pastor, he constructed a public school at Nisibis, in which he himself was an instructor. He made a strong impression on the hearts of his listeners by the high morality of his life.

Saintt Gregory, Bishop of Great Armenia, turned to him with a request to write about the faith, and the Nisibis pastor sent to him by way of reply a detailed Discourse, 18 Chapters in length about the faith, about love, fasting, prayer, spiritual warfare, the resurrection of the dead, the duties of pastors, about circumcision against the Jews, about the choice of foods, about Christ as the Son of God, and so on. His composition distinguishes itself by its persuasive clear exposition and warmth.