Against the redoubtable combination of gendarmes and Swiss mercenary pikemen in the French force, the allies had only Neapolitan troops of indifferent quality and a small corps of lightly-armed Spanish soldiers, accustomed to fighting the Moors of Spain.

The battle is notable primarily because it is often cited as the prime reason for the reorganization of the Spanish army,[2][3] which brought about widespread adoption of firearms in pike and shot formations, one of the milestones of the "Military Revolution."

On 30 May 1495 Charles split his army, taking half of the troops (approximately 9,000 men, horse and foot) in the northward march to fight their way back into France, and leaving the rest to hold the recently conquered Neapolitan territories.

Fernández De Córdoba had been selected by Queen Isabella to lead the Spanish contingent because he was a favorite of the court as well as a soldier of considerable renown, despite his relative youth.

Fernández De Córdoba arrived in the port at Messina on 24 May 1495, only to find that Ferdinand II of Naples had already crossed into Calabria with an army, borne upon the fleet of Admiral Requesens, and had reoccupied Reggio.

The League of Venice assisted the allies by sending a Venetian fleet under Admiral Antonio Grimani to raid along the eastern coast of French-occupied Naples.

Upon hearing the news that d’Aubigny was approaching, but unaware that Précy and the Swiss mercenaries had joined him, Ferdinand II of Naples decided to meet the French in battle immediately, a decision shared by the Spanish and Neapolitan nobility.

However, at this point the Calabrian militia panicked—possibly misconstruing the withdrawal of the jinetes as a rout, possibly fleeing the oncoming Swiss pike force—and fell back, exposing the left flank of the allied army.

Fernández De Córdoba, using what amounted to guerrilla tactics, and carefully avoiding any direct encounter with the dreaded Swiss battalions or massed gendarmes, slowly retook the rest of Calabria.

Fernández De Córdoba's disastrous encounter at Seminara with the melee-proficient French/Swiss force led eventually to his introduction of the mixed pike and shot army (the tercios born).