| Italian War of 1564–1572 | |||||||||
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| Part of the Italian Wars | |||||||||
 The Battle of Busseto in 1568 by Giorgio Vasari |
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 France
|  Spain
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| Commanders and leaders | |||||||||
| Charles IV
| Count of Alba
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The Italian War of 1564–1572 was a conflict in the Italian Wars largely between France under Henry III and Spain. The conflict saw extensive fighting in the Italian peninsula, as well as attempted invasions of Spain and Africa. The conflict would end largely inconclusively, while proving ruinously expensive for the major participants.
The war began four years following the Treaty of Rome that concluded the War of the League of Rimini. Under this arrangement the House of Arpad had largely been rebuked from northern Italy, leaving a power vacuum exploited by the Spanish. The Spanish directly occupied Modena with Papal backing, leading to states such as Florence and Genoa seeking French protection in case of further Spanish expansion. In 1564 Spain supported the Insubrian Republic’s invasion of Florence, prompting a French invasion of Italy. Less than a year into the war the unexpected death of Charles IV and the succession of his young son as Henry III derailed French war efforts, allowing Spain to claim victory over Florence by the end of the year.
Spain laid claim to Florence, soaring relations with the Insubrian Republic and other Italian powers. The Papacy left the Spanish alliance and created a new coalition along with Venice, which sought to contain the Spanish. The Insubrian Republic effectively became a Spanish puppet after a corrupt election in 1566, later allowing French chief minister René de l'Hôpital to persuade the Florentine-born military commander of Milan, Piero Strozzi, to defect in exchange for French recognition of his rule over a reformed Duchy of Milan. Under the leadership of Strozzi and Charles Amadeus of Savoy, the Italian alliance managed to capture Milan in 1568. l'Hôpital also renewed the controversial Franco-Abbasid alliance, leading to a Muslim naval campaign and a disastrous Spanish attempt to seize Algiers. The Franco-Spanish theatre in southern France, the latter eventually joined by Arles, ended inconclusively, as did an attempted English attack in the Lowlands.
The war would conclude with a series of treaties in 1572, which saw the Spanish repulsed from Milan and the ascension of the Strozzi dynasty. The conflict would prove immensely costly for both sides; France in particular was destabilized but nonetheless survived, and the reign of Henry III would be marked by numerous other wars against the Spanish and English.
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