Born in Machelen, he probably received his early musical education at Antwerp. By 1536 he arrived in Italy. From 1540 to 1545, he was chorister at St. Mark's in Venice, where he studied under Willaert.
In 1547, he entered in the service of duke Ercole II d'Este in Ferrara as choir master. Giaches de Wert was one of his pupils there.
When Ercole died in 1559, de Rore offered his services to his successor Alfonso, but the new duke refused and appointed Francesco della Viola instead.
From 1560 until 1563, de Rore worked for Margaret of Parma in Brussels and for her husband Ottavio Farnese in Parma. In 1562 he was appointed choir master of St. Mark's in Venice, but he resigned in 1564 and returned to Parma, where he died.
The most influential of the early madrigalists, De Rore wrote over 120 madrigalss, as well as around 80 sacred motets, 3 masses, a Passion, psalms, secular motets and chansons.