Much of Charles's reign was taken up with wars with France, which found itself encircled by Charles's empire and still maintained ambitions in Italy. The
first war with Charles's great nemesis
Francis I of France began in
1521. Charles allied with England and
Pope Leo X against the French and the Venetians, and was highly successful, driving the French out of
Milan and defeating and capturing Francis at the
Battle of Pavia in
1525. To gain his freedom, the French king was forced to cede
Burgundy to Charles in the humiliating
Treaty of Madrid (1526).
When he was released, however, Francis had the Parlement of Paris denounce the treaty because it had been signed under
duress. France then joined the
League of Cognac that the
Pope had formed with
Henry VIII of England, the Venetians, the Florentines, and the Milanese to resist imperial domination of Italy. In the ensuing war, Charles's
sack of Rome (1527) and virtual imprisonment of
Pope Clement VII in 1527 prevented him from annulling the marriage of
Henry VIII of
England and Charles's aunt
Catherine of Aragon, with important consequences. In other respects, the war was inconclusive. In the
Treaty of Cambrai (1529), called the "Ladies' Peace" because it was negotiated between Charles's aunt and Francis's mother, Francis renounced his claims in Italy but retained control of Burgundy.
A
third war erupted in
1535, when, following the death of the last Sforza
Duke of Milan, Charles installed his own son,
Philip, in the duchy, despite Francis's claims on it. This war too was inconclusive. Francis failed to conquer Milan, but succeeded in conquering most of the lands of Charles's ally the
Duke of Savoy, including his capital,
Turin. A truce at
Nice in
1538 on the basis of
uti possidetis ended the war, but lasted only a short time.
War resumed in
1542, with Francis now allied with Ottoman Sultan
Suleiman I and Charles once again allied with
Henry VIII. Despite the conquest of
Nice by a Franco-Ottoman fleet, the French remained unable to advance into Milan, while a joint Anglo-Imperial invasion of northern France, led by Charles himself, won some successes but was ultimately abandoned, leading to another peace and restoration of the
status quo ante in
1544.
A
final war erupted with Francis's son and successor,
Henry II, in
1551. This war saw early successes by Henry in
Lorraine, where he captured
Metz, but continued failure of French offensives in Italy. Charles abdicated midway through this conflict, leaving further conduct of the war to his son,
Philip II and his brother,
Ferdinand I, Holy Roman Emperor.
