The Italian Wars were a series of wars from 1494 to 1559 for control over the States of Italy , mainly involving France and Spain, but also involving most other European states, and the imprisonment for several months of Pope Clement VII.
They started with the plotting of Ludovico Sforza of Milan also known as "Ludovico il Moro" encouraging French involvement.
Charles VIII of France was encouraged by Ludovico to reassert the Angevin claim to the throne of Naples, then under Aragonese control. Ferdinand I of Naples died in 1494. and the French were welcomed into Florence by Savonarola and into Rome. They soon proved unpopular in Italy, and the League of Venice was formed against them, Charles being defeated at the Battle of Fornovo, but escaping to France.
His cousin and successor Louis XII of France invaded Italy in 1499 and managed to hold the north of the country, agreeing to partition Naples with Ferdinand II of Aragon. The two powers had fallen out by 1502, and the French were expelled from the south, retaining their occupation of Milan.
Meanwhile, Pope Julius II was more concerned with curbing the territorial expansion of Venice, and in 1508 formed the League of Cambrai, in which France, the Papacy, Spain and the Empire agreed to restrain the Venetians. At the Battle of Agnadello in 1509, the Venetians were defeated. But in the following year, Julius reached a modus vivendi with Venice, and, seeing France as a more dangerous power, formed the Holy League to expel the “barabarians”.
Charles V, Holy Roman Emperor was determined to end the French possession of Milan, something finally accomplished at the Battle of Pavia in 1525. Francis was taken hostage, and imprisoned in Madrid until he made concessions over Italy (which he later claimed were made under duress). Pope Clement VII, alarmed at the power of the Empire, allied the Papacy with France, giving rise to the Sack of Rome by imperial troops in 1527. While this caused Charles some embarrassment, it enabled him to keep the Pope from annulling the marriage of Henry VIII of England and Catherine of Aragon, though in turn this lead to the Schism of the Church of England with Rome.
The Italian Wars had a number of impacts on the work and workplace of Leonardo da Vinci, for example scuppering his plans for a "Gran Cavallo" horse statue in 1495 when the seventy tons of bronze were instead cast into weapons to save Milan.