Luis de Requesens y Zúñiga was born at Molins de Rei. He, and his brother Juan de Zúñiga y Requesens, were the sons of Juan de Zúñiga, a tutor of king Philip II, and Estefanía de Requesens. He married Gerónima Esterlich y Gralla, the daughter of Francisco Gralla, "Maestre Racional" or Finances Head Controller in Catalonia.
His early career was that of a government official and diplomat. In 1563 he gained the king's confidence as his representative at Rome. In 1568 he was appointed lieutenant-general to John of Austria during the suppression of the Morisco Revolt in the Alpujarras, and he also accompanied John during the Lepanto campaign, his function being to watch and control his nominal commander-in-chief, whose excitable temperament was distrusted by the king.
In 1572 Philip named him Governor of the Duchy of Milan, a post usually given to a great noble. Requesens was only a gentleman, though by the king's favour he was grand commander of the military order of Santiago in Castile. He was credited with having shown moderation at Milan, but he came into sharp collision with the archbishop, Charles Borromeo, who took up the cause of his flock.