The Synaxarion calls him "Our Father Cassian, chosen by God to bring the illumination of Eastern monasticism to the West". He was born in Scythia of noble parents, and was well educated in secular things. But, thirsting for perfection, he left all behind and travelled with his friend Germanus to the Holy Land, where he became a monk in Bethlehem. After becoming established in the monastic life for several years, St John felt a desire for greater perfection, and sought out the Fathers of the Egyptian Desert. He spent seven years in the Desert, learning from such Fathers as Moses, Serapion, Theonas, Isaac and Paphnutius. Through long struggles in his cell, St John developed from personal experience a divinely-inspired doctrine of spiritual combat. Many say that it was he who first listed the eight basic passions: gluttony, fornication, avarice, anger, sadness, acedia, vainglory and pride.

In time, struggles in the Alexandrian Church made life so difficult for the Egyptian monks that St John (still accompanied by his friend Germanus), sought refuge in Constantinople, where they came under the care and protection of St John Chrysostom. When the holy Archbishop was exiled, St John once again fled, this time to Rome, where he came under the protection of Pope Innocent I. This proved to be providential for the Western Church, for it was St John who brought the treasures of Desert spirituality to the monasteries of the West. He founded the monastery of St Victor in Marseilles, then, at the request of his bishop, wrote the Cenobitic Institutions, in which he adapted the austere practices of the Egyptian Fathers to the conditions of life in Gaul. He went on to write his famous Conferences, which became the main channel by which the wisdom of the desert East was passed to the monastics of the West. Saint Benedict developed much of his Rule (which at one time governed most monasteries in the Latin world) from St John's Institutions,, and ordered that the Conferences be read in all monasteries.

Saint John reposed in peace in 435, and has been venerated by the monks of the West as their Father and one of their wisest teachers. His relics are still venerated at the Abbey of St Victor in Marseilles.

St John's writings were soon attacked by extreme Augustinians and, as Augustinianism became the official doctrine of the Latin Church, his veneration fell out of favor in the West. Outside the Orthodox Church, his commemoration is now limited to the diocese of Marseilles.