He was born in Rome to a wealthy senatorial family. He received a good education in secular and spiritual learning, and became Prefect of Rome. While still in the world, he used his great wealth mostly for the good of the Church, building six monasteries in Sicily and another in Rome itself. At this monastery, dedicated to the Apostle Andrew, Gregory was tonsured a monk. He was appointed Archdeacon of Rome, then, in 579, Papal legate to Constantinople, where he lived for nearly seven years. He returned to Rome in 585 and was elected Pope in 590.

He is famed for his many writings, his generous charity (he gave almost all his income to the poor, and often invited the poor to share his table), and for initiating missionary work among the Anglo-Saxon peoples. The Liturgy of the Presanctified Gifts, celebrated on Wednesday and Friday evenings during Great Lent, was compiled by him. St Gregory introduced elements of the chanting that he had heard in Constantinople into Western Church chant: The Gregorian Chant which beautified the Western churches for many years is named for him. Its system of modes is related to the eight tones of the Eastern church. He is called 'the Dialogist' after his book The Dialogues, an account of the lives and miracles of Italian saints.

Saint Gregory reposed in peace in 604.