War of the League of Cognac The War of the League of Cognac ( 1526 – 30 ) was fought between the Habsburg dominions of Charles V — primarily Spain and the Holy Roman Empire — and the League of Cognac , an alliance including France , Pope Clement VII , the Republic of Venice , England , the Duchy of Milan and Republic of Florence . Prelude . Shocked by the defeat of the French in the Italian War of 1521 , Pope Clement VII , together with the Republic of Venice , began to organize an alliance to drive Charles V from Italy . Francis , having signed the Treaty of Madrid , was released and returned to France , where he quickly announced his intention to assist Clement . Thus , in 1526 , the League of Cognac was signed by Francis , Clement , Venice , Florence , and the Sforza of Milan , who desired to throw off the Imperial hegemony over them . Henry VIII of England , thwarted in his desire to have the treaty signed in England , refused to join . Initial moves . The League quickly seized Lodi , but Imperial troops marched into Lombardy and soon forced Sforza to abandon Milan . The Colonna , meanwhile , organized an attack on Rome , defeating the Papal forces and briefly seizing control of the city in March 1526 ; they were soon paid off and departed , however . Rome . Charles V now gathered a force of landsknecht s under Georg Frundsberg and a Spanish army under Charles of Bourbon ; the two forces combined at Piacenza and advanced on Rome . Francesco Guicciardini , now in command of the Papal armies , proved unable to resist them ; and when the Duke of Bourbon was killed , his underpaid army sacked the city , forcing the Pope to flee . Naples . The looting of Rome , and the consequent removal of Clement from any real role in the war , prompted frantic action on the part of the French . On 30 April 1527 , Henry VIII and Francis signed the Treaty of Westminster , pledging to combine their forces against Charles . Francis , having finally drawn Henry VIII into the League , sent an army under Odet de Foix and Pedro Navarro , Count of Oliveto through Genoa — where Andrea Doria had quickly joined the French and seized much of the Genoese fleet — to Naples , where it proceeded to dig itself in for an extended siege . Genoa . Doria , however , soon deserted the French for Charles . The siege collapsed as plague broke out in the French camp , killing most of the army along with Foix and Navarro . Andrea Doria ' s offensive in Genoa ( where he soon broke the blockade of the city and forced the surrender of the French at Savona ) , together with the decisive defeat of a French relief force under Francis de Bourbon , Comte de St . Pol at the Battle of Landriano , ended Francis ' s hopes of regaining his hold on Italy . Barcelona , Cambrai , and Bologna . Following the defeat of his armies , Francis sought peace with Charles . The negotiations began in July 1529 in the border city of Cambrai ; they were conducted primarily between Francis ' s mother Louise of Savoy for the French and her sister - in - law , Margaret of Austria for her nephew the Emperor ( leading to its being known as the " Paix des Dames " ) , Charles himself having sailed from Barcelona to Italy shortly before . The final terms largely mirrored those of the Treaty of Madrid three years earlier ; Francis surrendered his rights to Artois , Flanders , and Tournai , and was obliged to pay a ransom of two million golden écu s before his sons were to be released . Removed , however , were both the humiliating surrender of Burgundy itself and the various points dealing with Charles de Bourbon , who , having been killed two years prior , was no longer a candidate for leading an independent Kingdom of Provence . The final treaty , signed on 5 August , removed France from the war , leaving Venice , Florence , and the Pope alone against Charles . Charles , having arrived in Genoa , proceeded to Bologna to meet with the Pope . Clement absolved the participants of the sack of Rome and promised to crown Charles . In return , he received Ravenna and Cervia ; cities which the Republic of Venice was forced to surrender — along with her remaining possessions in Apulia — to Charles in exchange for being permitted to retain the holdings she had won at Marignano . Finally , Francesco was permitted to return to Milan — Charles having abandoned his earlier plan to place Alessandro de ' Medici on the throne , in part due to Venetian objections — for the sum of 900 , 000 scudi . Florence . The Republic of Florence alone continued to resist the Imperial forces , which were led by the Prince of Orange . A Florentine army under Francesco Ferruccio engaged the armies of the Emperor at the Battle of Gavinana in 1530 , and , although the Prince of Orange himself was killed , the Imperial army won a decisive victory and the Republic of Florence surrendered ten days later . Alessandro de ' Medici was then installed as Duke of Florence .