As first prince of the blood, Charles was a prominent figure in the early part of his brother-in-law's reign. Made governor of Normandy, Charles fought at Marignano in 1515, and in 1521 defended Champagne against an imperial invasion. He accompanied his brother-in-law, King Francis, on his second expedition to Italy in 1525, and after the disaster at Pavia, took command of the defeated French forces, leading them in retreat back to French territory. He was made a scapegoat for the defeat and accused of abandoning the king, and died soon after. Although Charles had a sister, Françoise, who survived him, his widow took possession of his lands after his death.