Charles II Gonzaga was the son of Charles of Gonzaga-Nevers of Rethel, Nevers, Mantua, and Montferrat; and Maria Gonzaga. He followed his grandfather Charles I, Duke of Mantua, in 1637 as ruler of these lands, the first ten years under regency of his mother Duchess Maria. On 22 March 1657, Charles II received the appointment as Imperial Vicar in Italy. Charles sold the Duchies of Nevers and Rethel in 1659 to Cardinal Jules Mazarin, the de facto Regent of France, and they became part of France.