John, the son of a high-ranking military officer, was brought up as a Christian by his widowed mother and was intended for the law, to which end he studied under a distinguished pagan rhetorician, Libanius. But John also studied theology, and before long he gave up his profession to become a hermit-monk. This life was not for him, either. His health gave way, and he returned to Antioch, becoming an ordained deacon and priest there. For 12 years (from 386) he established himself as a great preacher, his homilies (sermons) including some on the first and fourth Gospels and on eight of St. Paul's letters. A sensational episode of this period was a riot in 387, during which the citizens of Antioch treated the images of the sacred emperors with disrespect and were threatened with reprisals; in a famous course of sermons, “On the Statues,” Chrysostom set himself to bring his hearers to a frame of mind suitable both to the season, Lent, and to the dangerous situation in which they stood. His reputation as a preacher was now assured. His brilliant exposition and moral teaching have the note of universality; his words strike the reader today as forcefully as ever, and his humorous sallies are as pungent as when they provoked laughter in the congregations of Antioch and Constantinople. He was concerned, above all, for the spiritual and temporal welfare of the needy and oppressed. He was not alone among the early Fathers in speaking out against the abuse of wealth, teaching that personal property is not strictly private but a trust, and declaring that what was superfluous to one's reasonable needs ought to be given away. But none surpassed John Chrysostom in his eloquent, moving, and repeated insistence on almsgiving.

In 398 Chrysostom was called to Constantinople to be its archbishop, much against his will. There he gained a large following among the people, but his castigation of the misuse of riches angered the wealthy and influential. An unscrupulous alliance against John was made by Eudoxia, the wife of the Eastern Roman emperor Arcadius, and the archbishop of the rival see of Alexandria, the powerful Theophilus (Theophilus of Alexandria, Saint). In 403 Theophilus convened a synod of disaffected or subservient Syrian and Egyptian bishops at The Oak, across the Bosporus. This gathering indicted John on a large number of charges, many of which were purely frivolous or vexatious. Chrysostom refused to appear before the synod, whereupon it condemned him and professed to depose him from his see. The emperor Arcadius therefore banished Chrysostom from the city, recalled him at once, and finally banished him again in the following year. He was kept in confinement at Cucusus in Armenia.

Chrysostom appealed his banishment to the bishop of Rome, Pope Innocent I (Innocent I, Saint); the latter, with the help of the Western emperor Honorius, attempted to intervene, but his efforts were brought to nothing by Chrysostom's enemies. In exile, however, John found it possible to keep up a lively correspondence with his supporters and was still able to exert a measure of influence in his cause, and word came from Constantinople that he was to be removed to an even more remote place at the eastern end of the Black Sea. Chrysostom did not survive the exhausting journey. The official rehabilitation of John Chrysostom came about 31 years later, when his relics were brought from Comana to Constantinople and were solemnly received by the then archbishop Proclus and the emperor Theodosius (Theodosius I) II, son of Arcadius and Eudoxia.

Chrysostom was not an outstanding theologian or theological writer; it has been said that a detailed history of Christian theology could be written without mentioning his name. He was a superb orator, though. In his sermons he seldom used allegory but spoke plainly and combined penetration into the meaning of Scripture with a genius for its personal application. Each of his sermons had its moral or social lesson. His works consist of a large number of scriptural homilies and other sermons, together with some treatises and letters.

The most frequently used of the three eucharistic services of the Eastern Orthodox church is called the Liturgy of St. John Chrysostom, but the evidence that he had anything to do with its composition is unconvincing. The Prayer of St. John Chrysostom in The Book of Common Prayer (Book of Common Prayer) of the Church of England is taken from this liturgy, hence the attribution of the prayer.