Cephalonia, one of the Ionian Islands off the western coast of Greece, had been in the hands of the Italian counts palatine of the Tocco family until 1479, when it was captured by the Ottoman Empire during the First Ottoman–Venetian War.

The war continued to go badly for Venice, as the Ottomans shifted their attention to the Morea and stormed Modon on 9 August 1500, followed by the surrender thereupon of the neighbouring forts Coron and Navarino.

[3] On 17 August 1500, however, the Spanish captain-general, Gonzalo Fernández de Córdoba, offered the forces at his disposal to the aid of Venice.

Aided by the Spanish fleet, the newly appointed Venetian captain-general of the Sea, Benedetto Pesaro, landed on Cephalonia and after a siege took the island's capital, the Castle of St. George, on 24 December.

When a peace treaty was concluded in Constantinople in December 1502, Cephalonia remained in Venetian hands, but Lefkada was returned to Ottoman rule in 1503.