In 1613 Charles also became Prince-Bishop of Brixen, however, he left the governance of the diocese to an administrator as he had chosen Neisse (Nysa) for his permanent residence.

Upon his appointment as Breslau prince-bishop, he strongly protested against the 1609 Letter of Majesty, issued by his cousin Emperor Rudolf II to treat all religions equally in the Bohemian crown land of Silesia, and failed to succeed as a Silesian Landeshauptmann governor.

After he had received the Bohemian County of Kladsko from Emperor Ferdinand II in 1621, he had the area likewise occupied by Imperial troops and forcefully reverted to Catholicism.

In 1624 he travelled to Madrid, at the request of his nephew King Philip IV of Spain, who planned to appoint him Viceroy of Portugal.

His mortal remains were buried in the Royal Site of San Lorenzo de El Escorial, while his heart was transferred to the newly erected St Mary's Jesuit Church in Nysa.