16th Century: League of Cambria, Lepanto, and loss of Cyprus (jan 1, 1500 – dec 31, 1599)

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At the turn of the century, alliance with Louis XII of France against Milan gained Venice Cremona. The Ottomans attacked Lepanto and defeated Venice in the Battle of Zonchio, before sacking Friuli again. Preferring peace to total war, Venice surrender Lepanto, Modon, and Coron. In 1508, eager to take Venetian lands, all neighboring powers joined in the League of Cambria under the leadership of Pope Julius II. An offensive was launched and at the Battle of Agnello, Venice was crushingly defeated in one of the low point of Venetian history. French and Imperial troops temporarily occupied Venice. Spain and the Pope broke off their alliance with France, and much of the territory lost was regained. Defeat had turned to victory, but this marked the end of Venetian expansion. Spain won the struggle with France over supremacy in Italy, putting Venice between Spanish and Turkish superpowers. They would adopt a skillful strategy of quasi-neutrality, which would shift to a defensive stance against Ottomans. In the Third Venetian-Ottoman War, Pope Paul III resolved to form a Holy League in 1538 to defend against expected Ottoman aggression, with the Holy Roman Empire, Spain and Venice joining. The war was particularly painful for the Venetians who lost most of their remaining foreign holdings and showed they could no longer take on the Ottomans alone. The supremacy of the sea passed to the Ottomans. In the Fourth Venetian-Ottoman War from 1570-73, the Ottomans took Cyprus before seeing their fleet destroyed in the Battle of Lepanto by the new Holy League, a Venetian, Spanish, and Holy Roman alliance. The peace treaty left Cyprus in the hands of the Ottomans.

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