The exact date of Gregory's birth is uncertain, but is usually estimated to be around the year 540, in the city of Rome, then recently reconquered by the Eastern Roman Empire from the Ostrogoths. His parents named him Gregorius, which according to Ælfric of Abingdon in An Homily on the Birth-Day of S. Gregory, "... is a Greek Name [sic], which signifies in the Latin Tongue, Vigilantius, that is in English, Watchful...." The medieval writer who provided this etymology did not hesitate to apply it to the life of Gregory. Ælfric states, "He was very diligent in God's Commandments."
Gregory was born into a wealthy patrician Roman family with close connections to the church. His father, Gordianus, who served as a senator and for a time was the Prefect of the City of Rome, also held the position of Regionarius in the church, though nothing further is known about that position. Gregory's mother, Silvia, was well-born, and had a married sister, Pateria, in Sicily. His mother and two paternal aunts are honored by Catholic and Orthodox churches as saints. Gregory's great-great-grandfather had been Pope Felix III, the nominee of the Gothic king, Theodoric. Gregory's election to the throne of St Peter made his family the most distinguished clerical dynasty of the period.
The family owned and resided in a villa suburbana on the Caelian Hill, fronting the same street (now the Via di San Gregorio) as the former palaces of the Roman emperors on the Palatine Hill opposite. The north of the street runs into the Colosseum; the south, the Circus Maximus. In Gregory's day the ancient buildings were in ruins and were privately owned. Villas covered the area. Gregory's family also owned working estates in Sicily and around Rome. Gregory later had portraits done in fresco in their former home on the Caelian and these were described 300 years later by John the Deacon. Gordianus was tall with a long face and light eyes. He wore a beard. Silvia was tall, had a round face, blue eyes and a cheerful look. They had another son whose name and fate are unknown.
Gregory was born into a period of upheaval in Italy. From 542 the so-called Plague of Justinian swept through the provinces of the empire, including Italy. The plague caused famine, panic, and sometimes rioting. In some parts of the country, over 1/3 of the population was wiped out or destroyed, with heavy spiritual and emotional effects on the people of the Empire. Politically, although the Western Roman Empire had long since vanished in favour of the Gothic kings of Italy, during the 540s Italy was gradually retaken from the Goths by Justinian I, emperor of the Eastern Roman Empire ruling from Constantinople. As the fighting was mainly in the north, the young Gregory probably saw little of it. Totila sacked and vacated Rome in 546, destroying most of its population, but in 549 he invited those who were still alive to return to the empty and ruined streets. It has been hypothesized that young Gregory and his parents retired during that intermission to their Sicilian estates, to return in 549. The war was over in Rome by 552, and a subsequent invasion of the Franks was defeated in 554. After that, there was peace in Italy, and the appearance of restoration, except that the central government now resided in Constantinople.
Like most young men of his position in Roman society, Saint Gregory was well educated, learning grammar, rhetoric, the sciences, literature, and law, and excelling in all. Gregory of Tours reported that "in grammar, dialectic and rhetoric ... he was second to none...." He wrote correct Latin but did not read or write Greek. He knew Latin authors, natural science, history, mathematics and music and had such a "fluency with imperial law" that he may have trained in it "as a preparation for a career in public life". Indeed, he became a government official, advancing quickly in rank to become, like his father, Prefect of Rome, the highest civil office in the city, when only thirty-three years old.
The monks of the Monastery of St. Andrew, established by Gregory at the ancestral home on the Caelian, had a portrait of him made after his death, which John the Deacon also saw in the 9th century. He reports the picture of a man who was "rather bald" and had a "tawny" beard like his father's and a face that was intermediate in shape between his mother's and father's. The hair that he had on the sides was long and carefully curled. His nose was "thin and straight" and "slightly aquiline". "His forehead was high." He had thick, "subdivided" lips and a chin "of a comely prominence" and "beautiful hands".
In the modern era, Gregory is often depicted as a man at the border, poised between the Roman and Germanic worlds, between East and West, and above all, perhaps, between the ancient and medieval epochs.