John was trained in rhetoric at Antioch under the pagan orator Libanius, spent years as an ascetic in the hills outside the city, and returned with his health broken to be ordained and to preach. The Antiochene years produced most of the homilies that made his reputation, working through Genesis, the Psalms, Matthew, John and the letters of Paul verse by verse, and they are the reason his name survived: J. N. D. Kelly's biography notes that more manuscripts of Chrysostom survive than of any other Greek father.
In 398 he was taken to Constantinople, effectively against his will, and made archbishop. He preached in the capital the way he had preached in Antioch, which turned out to be a different act. He attacked the wealth of the rich and the display of the court, he cut the episcopal household budget and gave the money to hospitals, he intervened against bishops in Asia Minor whom he found guilty of selling ordinations, and he made enemies at every level, including the empress Eudoxia.
In 403 a synod convened outside Chalcedon, remembered as the Synod of the Oak, deposed him on a list of charges assembled by Theophilus of Alexandria. He was recalled almost at once after public disorder and an earthquake, deposed again the following year, and sent into exile in Armenia, from which he kept up a correspondence. In 404 the order came to move him further, to the eastern edge of the Black Sea, and he died on the road at Comana in 407.