In 1494, there were five sovereign regional powers in Italy: Milan, Venice, Florence, the Papal States and Naples. In 1536, only one remained: Venice. These decades of conflict precipitated great anxiety among Western thinkers, and Italians responded to the fragmentation of Latin Christendom, the end of self-governance for Italians, and the beginning of the early modern era in various ways. They were always heavily influenced by the lived experience of warfare between large Christian armies on the peninsula. The diplomatic and military history of this 30-year period is a complex one that one eminent Renaissance historian, Lauro Martines, has described as "best told by a computer, so many and tangled are the treatises, negotiations and battles." At the same time, the fighting went in tandem with the Renaissance and was influenced by it.

Before 1494, death tolls were counted in hundreds rather than thousands, but that would change over the next generation, and among the many battles fought, few stood out like the Battle of Ravenna in 1512. Ravenna is an ancient city in northern Italy on the Adriatic Coast that replaced Rome as capital of the Western Roman Empire for much of the 5th century and continued to serve as a regional center for its successor states, including the Ostrogoths, Byzantines, and Papal States. On April 11 of that year, two great armies met near Ravenna, which had been the site of conflict at least six times before on account of its strategic importance. It was a well-protected city with connections to rich Mediterranean ports, and it guarded the routes to central and southern Italy. Over 44,000 troops gathered, a vast number for the time, to fight over Italy's destiny, which had become important to France, Austria, and Spain, the great powers of the time.