Francis I's First Invasion of Italy (1515-16) was the most successful of his many campaigns in Italy, and saw him defeat the Swiss at Marignano and take control of the Duchy of Milan, expelling Massimiliano Sforza (Italian Wars, 1494-1559).
By the end of the War of the Holy League most of the major players in Italy were officially at peace with each other. France was allied with Venice, and at peace with Henry VIII of England. The Emperor Maximilian was allied with Pope Leo X, while Ferdinand II of Aragon, Massimiliano Sforza, duke of Milan and his Swiss protectors and Florence were all hostile to the French.
Francis inherited a sizable army from Louis XII, and also supplemented it with a force of landsknechts who ignored the Emperor's instructions not to fight for the French, and a contingent from the Spanish frontiers recruited by Pedro Navarra, an able Spanish engineer who had switched sides after his ransom went unpaid after he was captured at Ravenna.
The French began the campaign with around 30,000 men. Francis could also count on 12,000 Venetians under Bartolomeo Alviano. They were opposed by around 25,000 Swiss troops around Milan and 12,000 Spanish troops who were facing the Venetians around Lodi.
In August Navarra led the main French army across the normally unused Col d'Argentiere, while a second army advanced along the coast towards Genoa. The first French success came at Villafranca near Saluzzo (some way to the south of Turin), where they defeated a force of Italian cavalry under Prospero Colonna. The Swiss now began to argue amongst themselves. They had been guarding the passes north of Turin, but they now retreated to Vercelli, between Turin and Milan, where they continued to argue.
In early September Francis entered into negotiations with the Swiss, offering them money and Sforza lands in France in return for Milan. On 9 September around 10,000 of the Swiss accepted these terms and left for home, but a war party of at least 15,000 men remained in Italy, taking up a position at Monza, north of Milan. At this point the French were at Binasco, south of Milan. Francis's Venetian allies were near Cremona, some fifty miles to the east. The Spanish and Papal army was a little near Milan at Piacenza, but was split by the rivalry between their two commanders - Raymond of Cardona and Lorenzo de Medici.
On 10 September the French moved a short distance east to Marignano (Melegnano), while the Venetians moved north-west up the River Adda towards Lodi.
The war was decided by the battle of Marignano (13-14 September 1515). On the first day of the battle the Swiss attacked the French camp and a fierce struggle followed. At the end of the day the battle was still in the balance, and the fighting was renewed early on 14 September. The battle was decided by the arrival of Alviano with some of his cavalry in the rear of the Venetian force. The Swiss decided to retreat, and carried out an orderly withdrawal to Milan. On 16 September the surviving Swiss left Milan and began to retreat back home via Como. Pedro Navarro led a successful siege of the castle of Milan, and Massimiliano Sforza surrendered to the French, spending the rest of his life in comfortable exile.
This was the high point of Francis's career in Italy. The Swiss weren't entirely out of the war, but their enthusiasm had been badly dented. Pope Leo was ready to talk, and in December he met with Francis at Bologna and agreed a peace.
Maximilian still wanted to press his claim to Milan, and in March 1516 he invaded Lombardy with the support of five of the Swiss cantons. By now there were Swiss troops in the French army as well, and the Emperor's Swiss refused to fight their countrymen. Maximilian was forced to abandon yet another military campaign.
Early in the year Ferdinand II died, and was succeeded by his grandson Charles (Charles I of Spain at this point, but better known as the Emperor Charles V). The new king was willing to make peace with Francis, and on 13 August they agreed the Treaty of Noyon. Charles acknowledged the French claim to Milan in return for Francis renouncing his claim to Naples (not for the last time).
In November 1516 the Swiss League made an everlasting peace with France, which actually lasted until the French Revolution.
On 4 December 1516 the last of the major combatants made peace, when the Emperor Maximilian and Francis I agreed the Treaty of Brussels, although this was more of a truce than a potentially long-lasting peace treaty.
In the background the Venetians had continued to recover from their setbacks during the War of the League of Cambria, conquering Brescia, and regaining Verona just after the Treaty of Brussels.
The war ended with a false appearance of stability. Francis I was apparently secure in Milan. Charles I (V) had peacefully inherited Spain, Sicily and Naples and the Netherlands. Venice had recovered most of her mainland Empire. The Papal States were larger and more powerful than they had been for some time. Florence was now ruled by the Medici, who were closely allied with the Pope. This period of stability would be short-lived - the election of Charles I as the Emperor Charles V would trigger a life-long rivalry with Francis I, with the Emperor wanting to establish a universal monarchy and Francis angry that he had failed to win the Imperial crown himself. In 1521 the first of five Hapsburg-Valois Wars would break out, and by the time they came to an end in 1559 Spain would be established as the major power in Italy.