Italian Wars
War of the League of Cambrai

On 18 October 1503, Pius III was replaced by Pope Julius II, who as ruler of the Papal States was concerned by Venetian power in northern Italy. This fear was shared by his home town of Genoa, which also resented its expulsion from the Po Valley, and Maximilian, whose acquisition of Gorizia in 1500 was threatened by Venetian possession of neighbouring Friuli. Milan, controlled by Louis XII, was a long-standing opponent of Venice, while Ferdinand II, now king of Naples, wished to regain control of Venetian ports on the southern Adriatic coast. Along with the Duchy of Ferrara, Julius united these disparate interests into the anti-Venetian League of Cambrai, signed on 10 December 1508.

Although the French largely destroyed a Venetian army at Agnadello on 14 May 1509, Maximilian failed to capture Padua and withdrew from Italy. Now seeing the power of Louis XII as the greater threat, in February 1510 Pope Julius made peace with Venice, followed in March by an agreement with the Swiss Cantons to supply him with 6,000 mercenaries. After a year of fighting in which Louis XII occupied large parts of the Papal States, in October 1511 Julius formed the anti-French Holy League, which included Henry VIII of England, Maximilian and Spain.

A French army defeated the Spanish at Ravenna on 11 April 1512, but their leader Gaston de Foix was killed, while the Swiss recaptured Milan and restored Ludovico's son Massimiliano Sforza as duke. The members of the League then fell out over dividing the spoils and the death of Pope Julius on 20 February 1513 left it without effective leadership. In March, Venice and France formed an alliance, but from June to September 1513 the League won victories at Novara and La Motta in Lombardy, Guinegate in Flanders and Flodden in England. Despite this, fighting continued in Italy, with neither side able to gain a decisive advantage.

On 1 January 1515, Louis XII died and was succeeded by his son-in-law, Francis I, who took up his predecessor's cause and routed the Swiss at Marignano on 13–14 September 1515. Combined with the unpopularity of Massiliano Sforza, victory allowed Francis to retake Milan and the Holy League collapsed as both Spain and Pope Leo X saw little benefit in fighting on. In the treaty of Noyon, signed on 13 August 1516, Charles I of Spain acknowledged Francis as Duke of Milan, while Francis "passed" his claim to Naples onto Charles. Left isolated, in December Maximilian signed the Treaty of Brussels, which confirmed French possession of Milan.
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