Compromised in the conspiracy of La Mole and Coconnat in 1574, he joined the party of the Malcontents headed by François, Duke of Alençon (younger brother of kings Charles IX and Henry III) in 1575.

Appointed lieutenant general of Upper Languedoc in 1580, he took part in the siege of Paris in 1590 after the accession of Henry IV to the throne, and conquered Stenay from the Catholic League in 1591.

In 1591 Henry IV married him to Charlotte de La Marck, heiress to the duchy of Bouillon and of the Principality of Sedan.

Compromised in the conspiracy of Biron in 1602, he fled to Geneva the following year and had to accept a French protectorate over his duchy of Bouillon in 1606.

His lodgings at the Charterhouse were hung with tapestries, including rooms for his teenage nephew Henri de La Trémoille.