He was a kinsman of Cardinal Hadrian Castellensis, a native of Castro in Etruria. His father's name is said to have been George Virgil; his great-grandfather, Anthony Virgil, "a man well skilled in medicine and astrology," had professed philosophy at the University of Paris, as did Polydore's own brother and protege John Matthew Virgil, at Pavia, in 1517. A third brother was a London merchant in 1511.
Polydore was born at Urbino, is said to have been educated at Bologna, and was probably in the service of Guido Ubaldo, Duke of Urbino, before 1498, as in the dedication of his first work, Liber Proverbiorum (April 1498), he styles himself this prince's client. Polydore's second book, De Inventoribus Rerum, is dedicated to Guido's tutor, Ludovicus Odaxius, from Urbino, in August 1499. After a period as chamberlain to Pope Alexander VI he came to England in 1501 as deputy collector of Peter's pence for the cardinal. As Hadrian's proxy, he was enthroned Bishop of Bath and Wells in October 1504. It was at the instigation of King Henry VII of England that he commenced his Historia Anglica--a work which, though apparently begun as early as 1505, was not completed till August 1533, the date of its dedication to Henry VIII, and was not published till 1534.
In May 1514 Polydore and his patron, the cardinal, are found supporting Wolsey's claims to the cardinalship, but he had lost Wolsey's favour before the year was out. A rash letter, reflecting severely on Henry VIII and Wolsey, was intercepted early in 1515, after which Polydore was cast into prison and supplanted in his collectorship (March and April). He had some powerful supporters; both Catherine de' Medici and Pope Leo X wrote to the king on his behalf, From prison he sent an abject and almost blasphemous letter to the offended minister, begging that the fast approaching Christmas--a time which witnessed the restitution of a world--might see his pardon also. He was freed before Christmas 1515, though he never regained his collectorship. In 1525 he published the first edition of Gildas, dedicating the work to Cuthbert Tunstall, Bishop of London.
Next year appeared his Liber de Prodigiis, dedicated from London (July) to Francesco Maria, Duke of Urbino. Somewhere about 1538 Polydore left England, and remained in Italy for some time. Ill-health, he claimed, prevented him on his return from making his daily notes on contemporary events. About the end of 1551 he went home to Urbino, where he appears to have died in 1555. He had been naturalized an Englishman on 22 October 1510, and had held several clerical appointments in England. In 1508 he was appointed archdeacon of Wells, and in 1513 prebendary of Oxgate in St Paul's Cathedral, both of which offices he held after his return to Urbino.
The first edition of the Historia Anglica (twenty-six books) was printed at Basel in 1534; the twenty-seventh book, dealing with the reign of Henry VIII down to the birth of Edward VI (October 1536), was added to the third edition of 1555. Polydore claims to have been very careful in collecting materials for this work, and takes credit for using foreign historians as well as English; for which reason, he remarks, the English, Scots and French will find things reported in his pages far differently from the way in which they are used to hearing them within their own countries. In his search for information he applied to James IV of Scotland for a list of the Scottish kings and their annals; but not even his friendship for Gavin Douglas could make him accept the historical theories of the latter, who traced the pedigree of the Scots down from the banished son of an Athenian king and Scotta the daughter of the Egyptian tyrant of the Israelites.
A similar scepticism made him doubt the veracity of Geoffrey of Monmouth, and thus called forth John Leland's Defensso Gallofridi and Assertio Incomparabilis Arlurii. This doubting instinct led to his being accused of many offences against learning, such as that of burning cartloads of manuscripts lest his errors should be discovered, of stealing books from libraries and shipping them off to Rome. It is mainly from the time of Henry VI, where contemporary records begin to fail, that Polydore's work is useful. He must have been personally acquainted with many men whose memories went back to the beginning of the Wars of the Roses. John Sherren Brewer was one of the first to shed doubt on his reliability as an authority for the reign of Henry VIII, and indeed his spite against Wolsey is evident; but it is impossible to read his social and geographical accounts of England and Scotland without gratitude for a writer who has preserved so many interesting details.
Polydore's Adagia (Venice, April 1498) was the first collection of Latin proverbs ever printed; it preceded Erasmus's by two years, and the slight misunderstanding that arose for the moment out of rival claims gave place to a sincere friendship. A second series of Biblical proverbs (553 in number) was dedicated to Wolsey's follower, Richard Pace, and is preceded by an interesting letter (June 1519), which gives the names of many of Polydore's English friends, from More and Archbishop Warham to Linacre and Tunstall. The De Inventoribus, treating of the origin of all things whether ecclesiastical or lay (Paris, 1499), originally consisted of only seven books, but was increased to eight in 1521. It was exceedingly popular, and was early translated into French (1521), German (1537), English (1546) and Spanish (1551). All editions, however, except those following the text sanctioned by Gregory XIII in 1576, are on the Index Expurgatorius.
The De Prodigiis also, achieved a great popularity, and was soon translated into Italian (1543), English (1546) and Spanish (1550). This treatise takes the form of a Latin dialogue between Polydore and his Cambridge friend Robert Ridley. It takes place in the open air, at Polydore's country house near London. Polydore's duty is to state the problems and supply the historical illustrations; his friend's to explain, rationalize and depreciate as best he can. Here, as in the Historia Anglica, it is plain that the writer prides himself specially on the excellence of his Latin, which in Sir Henry Ellis's opinion is purer than that of any of his contemporaries.