Charles was the possessor of several crowns and yet more claims to sovereignty which served as a basis for his attempt to establish a universal dynastic monarchy with Habsburg hegemony over Europe. His fiercest enemies were France and its king, Francis I.
France saw itself surrounded. To the south lay the Iberian heartland of Spain, a rising Great Power. Along the borders of France with the Holy Roman Empire to the north and east was the diverse agglomeration of territories that had passed into Habsburg dominion through the Burgundian inheritance.
The dukes of Burgundy, a collateral branch of the Valois, had died out in the male line following the death of Charles the Bold in 1477, and France, ruled by the House of Valois, occupied those Burgundian territories that had been fiefs of the French crown.
France also cemented its position in Italy, bringing Milan under its control. Francis then staked claim to territories in southern Italy, which since the end of the fifteenth century had been first part of the crown of Aragon and later of Spain as a whole.
Charles for his part derived claims on parts of southern France as heir to the crown of Aragon. In rivalry with Francis he also laid claim to Milan; in ancient and Mediterranean tradition, power over Italy was regarded as the key to hegemony in Europe, for which both monarchs felt themselves predestined.
The conflict ended in a war, fought on Italian and French soil. While Charles was unable to achieve any great successes in France, his army in Italy won a number of victories. At the Battle of Pavia in 1525 the French king was even taken prisoner by the Spanish. In 1526 Francis was forced to accept the terms of the Treaty of Madrid, renouncing his claims to Burgundy, Naples and Milan. After his release he immediately revoked his agreement to the terms that had been extracted from him under coercion. The situation was not finally resolved until the Peace of Cambrai in 1529, according to the terms of which France retained the old Burgundian territories while renouncing its claims to those in Italy.
Meanwhile the situation in Italy had escalated. The imperial troops, including German mercenaries, made their way down the peninsula without any effective leaders, sacking Rome in 1527. This had not been ordered by Charles and he distanced himself from it. However, it proved politically advantageous for him, as the Pope, one of Charles’s adversaries, was deprived of his power. Charles had thus proved his dominance in Italy.
Charles’s triumph was affirmed by his coronation as emperor by the pope in Bologna in 1530. After Milan had come under Habsburg dominion in 1535 and Charles’s troops had won a victory over the Turks at the Siege of Tunis, Charles found himself at the apogee of his power.