Born near Arezzo, Italy, he studied at Florence and went to Rome about 1402. Pope Boniface IX made him one of the Apostolic secretaries, a position he held under Innocent VII, Gregory XII, Alexander V, and Antipope John XXIII. The deposition of John XXIII in 1415 and the lengthy delays of the Council of Constance (1414-1418) gave him time to search the libraries of the monasteries of Germany and France for classical texts whose names were known to earlier humanists but which did not survive in Italy. He discovered long-unknown texts of Cicero, Quintilian, Vegetius, Manilius, Ammianus Marcellinus, Statius, and Petronius. He specialized in recognizing fragments of authors by their writing styles and revealing the lost works.
From June, 1453, Poggio was head of the chancery of Florence under the Medici.
In the way of many humanists of his time, Poggio himself wrote only in Latin, and translated works from Greek into that language. His letters are full of learning, charm, detail, and amusing personal attack on his enemies and colleagues. His history of Florence from 1350 to 1455 is much less interesting.
He died in Florence.