The foremost composer of the Middle Ages, Guillaume de Machaut (c1300-c1377) set the scene for the flourishing of polyphonic music in the Renaissance period.

Although most of his work was secular, he is best known for his Messe de Nostre Dame. Two settings of the full Mass are known to pre-date Machaut's, but his is the first to have been written by a single composer. Machaut's Mass was originally assumed to have been composed for the coronation of Charles V of France in 1364, but it is now thought to have been written earlier than that, possibly for performance at the Saturday Mass for the Virgin at Reims Cathedral, where both Machaut and his brother Jean were canons. Money was left in the brothers' will to ensure the Mass would continue to be performed there.

One of the undisputed masters of Renaissance polyphony, Giovanni Pierluigi da Palestrina (c1525-1594) spent his musical life at the heart of the Catholic church. He dedicated his first compositions to Pope Julius III, thereby winning himself a short-lived position as a singer in the Sistine Chapel. (He was married and was dismissed from the choir within a year, along with two other married singers, by the new Pope Paul IV.)

Palestrina went on to produce a huge body of sacred music, including more than 100 polyphonic settings of the Mass. The most famous of these is the Missa Papae Marcelli, which is often identified as the work that convinced the Council of Trent that complex polyphonic composition was compatible with the clear intelligibility of the liturgical texts being sung. When it was printed in 1567, the dedication of the Mass included the words "novo modorum genere", which has been loosely translated as "a new form of expression".