Catherine de Médicis gave him Alençon in 1566, and he bore the title of duc d'Alençon until 1576. Small and swarthy, ambitious and devious, but a leader of the moderate Roman Catholic faction called the Politiques, he secured in the general Treaty of Beaulieu (May 6, 1576) a group of territories that made him duc d'Anjou. He also courted Elizabeth I of England and even succeeded in negotiating with her a marriage contract (1579), which, however, was never concluded, even after two wooing visits to London (1579, 1581–82). Seeking also to exploit the unsettled conditions in the Netherlands during the Dutch revolt against Spanish rule, he had himself proclaimed duke of Brabant and count of Flanders (1581), but the titles remained fictitious.

Anjou's death in 1584, during the reign of the childless Henry III, made his distant cousin the Protestant Henry of Bourbon-Navarre (the future Henry IV) heir presumptive to the crown of France.