Charles Emmanuel was duke at a volatile time, and subsequently was involved in many political intrigues, mostly by his relationship on his mothers side with the House of Guise. The Duke of Guise was one of the leaders of the Catholic League opposing the Huguenots, and Charles Emmanuel sympathised with their cause. However, after the assassination of Henry I, Duke of Guise and his brother the Cardinal of Guise, Charles Emmanuel was imprisoned by the Huguenots in 1588, but was able to escape. He died at Annecy in 1595, leaving the Duchy of Nemour to his brother Henri de Savoie.