Dufay was chorister at the Cambrai cathedral (1409), entered the service of Carlo Malatesta of Rimini c. 1420, and in 1428 joined the papal singers. In 1426 he became a canon of Cambrai. After seven years with the Duke of Savoy he lived at Cambrai from about 1440 and supervised the music of the cathedral. He took a degree in canon law about 1445 and in 1446 became a canon of Mons. Dufay's surviving works include 87 motets, 59 French chansons, 7 Italian chansons, 7 complete masses, and 35 mass sections. He often used, and may have originated, the technique of fauxbourdon, a style of composition based on the sonorities of the third and sixth and derived from English descant, an improvisational practice.

During his Italian period Dufay composed a number of ceremonial motets for public celebrations, among them the election of Pope Eugenius IV (1431), the Treaty of Viterbo (1433), and the dedication of Brunelleschi's dome for Sta. Maria del Fiore, Florence (1436). For the brilliant “Feast of the Pheasant” held in 1454 by Philip the Good of Burgundy and intended to initiate a crusade to recapture Jerusalem, Dufay composed a lamentation for the Church in Constantinople.

Dufay's chansons, normally in three voices, deal with subjects such as springtime, love, and melancholy. Most use the poetic-musical forms of the ballade, rondeau, and virelai; a few are written in freer form.

Dufay's masses laid the foundation for the rapid musical development of the mass in the second half of the 15th century. His complete mass settings are in four voices and use a cantus firmus placed in the tenor line. His canti firmi include secular songs such as L'homme armé (used by many composers up to Palestrina) and his own ballade Se la face ay pale, and sacred melodies such as Ave Regina coelorum.

In these and other works of his Cambrai period Dufay perfected a graceful and expressive style that incorporated into continental music the sweet harmonies of the contenance angloise or “English manner” that according to Martin le Franc's Le Champion des Dames (c. 1440) he had adopted from John Dunstable. In his music he created the characteristic style of the Burgundian composers that links late medieval music with the style of later Franco-Flemish composers of the Renaissance.