He was the second son of René II, Duke of Lorraine, and Philippa of Guelders. He was educated at the French court of Francis I. At seventeen, Claude made an alliance to the royal house of France by a marriage with Antoinette de Bourbon (1493–1583), daughter of François, Count of Vendôme. Their pretensions and ambitions inspired distrust in Francis I, although he rewarded Guise's services by substantial gifts in land and money. The duke distinguished himself in the Luxembourg campaign in 1542, but for some years before his death he effaced himself before the growing fortunes of his sons.