He worked as a singer and a composer at various courts in Italy. From 1420 he was about 6 years at the service of the Malatesta in Rimini and Pesaro. In 1428 he became member of the Papal Choir in Rome, at the service of Pope Martin V and later also of Pope Eugenius IV.
In 1436 he composed the festive motets Nuper rosarum flores, which were sung at the inauguration of Brunelleschi's dome of the cathedral in Florence, where Eugenius lived in exile. He also composed Lamentationes on the fall of Byzantium in 1453.
In 1458, he returned to Cambrai, where he had been appointed canon of the cathedral, and spent the last part of his life there.
Dufay was influenced by John Dunstable. His works include masterpieces in both religious and secular genres: 22 motets, 3 magnificats, 7 complete masses (among which the famous parody mass L'Homme armé where the cantus firmus is based on a popular tune) and 28 individual mass movements, as well as 87 French chansons. He is considered the founder of the so-called Burgundian or First Netherlands School of polyphonic composers (1450-1550).