During the French Wars of Religion, Clément became fanatically religious and an ardent partisan of the Catholic League. Viewing Protestantism as heresy, he talked of exterminating the Huguenots and formed a plan to kill Henry III. His project was encouraged by some of the heads of the League, in particular Catherine de Guise, the Duchess Montpensier; he was assured of temporal rewards if he succeeded and of eternal bliss if he failed. Having obtained letters for the king, he left Paris on July 31, 1589, and reached Saint-Cloud, the headquarters of Henry, who was besieging Paris, on August 1, 1589.
He was admitted to the royal presence and while presenting his letters he told the king that he had an important and confidential message to deliver. The attendants then withdrew and, as he leaned in to whisper in Henry's ear, Clément mortally wounded him with a dagger which had been concealed beneath his cloak. The assassin was immediately killed by the returning attendants, but Henry died early in the morning on the following day. Clement’s body was later quartered and burned.
This deed, although seen as a fanatical, brutal assassination by supporters of Henry III, was viewed with far different feelings in Paris and by the partisans of the League. Clément was seen as a martyr and was praised by Pope Sixtus V. His praise was such that canonization was even discussed, although Clément achieved sainthood.