Charles VIII became king of France in 1483 while still a minor. His sister Anne of France and her husband, Peter of Bourbon, directed government during his early reign. They defeated a coalition of princes in the conflict known as the Mad War, defending the crown's authority against magnates who sought to recover influence after Louis XI's death.

Charles's marriage to Anne of Brittany in 1491 followed French military pressure on the duchy and the defeat of its earlier political alignments. The marriage brought the Breton succession into the French royal household, although Brittany's final incorporation into the kingdom came later. It also required Charles to abandon his planned marriage to Margaret of Austria and complicated relations with the Habsburgs.

He then pursued the French crown's inherited claim to Naples. To reduce threats elsewhere, he made agreements with neighboring rulers that included payments and territorial concessions. In 1494 he led an army into Italy, using powerful artillery and the peninsula's divisions to advance rapidly. He entered Naples in February 1495, but possession proved much harder to maintain than conquest.

An opposing coalition, the League of Venice, threatened his route home. Charles withdrew northward and fought through the coalition's army at Fornovo in July 1495. The French forces left behind in Naples could not retain the kingdom. The expedition brought no lasting Neapolitan throne, but inaugurated a prolonged series of wars in which France and other European powers competed for Italian territory.

Charles also transformed the royal residence at Amboise. He enlarged the medieval castle into a palace, with large towers and gardens reflecting Italian influence. These commissions connected the Italian expedition with changes in French court culture and patronage. He died at Amboise on April 7, 1498, leaving no surviving son; his cousin Louis of Orléans succeeded as Louis XII. His expedition left a lasting Italian conflict.