René was born in Breda, the only son of Count Henry III of Nassau-Breda and Claudia of Chalon. Claudia's brother, Philibert of Chalon, was the last Prince of Orange from the House of Chalon. When Philibert died in 1530, René inherited the Princedom of Orange on condition that he used the name and coat of arms of the Chalon-Orange family. History knows him therefore as René of Chalon instead of as "René of Nassau-Breda".
Coat of arms of René of Chalon as Prince of Orange. The 1st and 4th grand quarters show the arms of the Chalon-Arlay
(the gold bend) princes of Orange (the bugle). The blue and gold checkers represent the arms of Jeanne of Geneva, who married one of the Chalon princes. The 2nd and 3rd show the quarterings of Brittany
. The inescutcheon overall is his paternal arms quartered of Nassau and Breda.
René of Chalon married Anna of Lorraine (1522–1568) on 20 August 1540 at Bar-le-Duc. They had only one child, a daughter named Maria, who lived only 3 weeks and was buried in the Grote Kerk in Breda. He was made a knight of the Golden Fleece the same year.