- France, England, Ottoman Empire vs. Holy Roman Empire, Spain
- Italian States fought on both sides
- Preceded by Italic League collapse in 1492
- France invaded Naples in 1494
- France invaded Lombardy and Piedmont in 1503
- Ended with the Treaty of Cateau-Cambrésis in 1559
- France gained Calais and Three Bishoprics
- Spain gained Naples, Sicily and Milan