In 1537, commanding a large Ottoman fleet, Hayreddin Barbarossa captured a number of Aegean and Ionian islands belonging to the Republic of Venice, namely Syros, Aegina, Ios, Paros, Tinos, Karpathos, Kasos, and Naxos, thus annexing the Duchy of Naxos to the Ottoman Empire. He then unsuccessfully besieged the Venetian stronghold of Corfu and ravaged the Spanish-held Calabrian coast in southern Italy.

In the face of this threat, Pope Paul III in February 1538 in assembled a ’’Holy League’’, comprising the Papal States, Hapsburg Spain, the Republic of Genoa, the Republic of Venice, and the Knights of Malta, to confront Ottoman fleet under Barbarossa.

The Ottoman won the battle at Preveza and, with the subsequent victory in the Battle of Djerba in 1560, the Ottomans succeeded in repulsing the efforts of Venice and Spain, the two principal rival powers in the Mediterranean, to stop their drive for controlling the sea. The Ottoman supremacy in large-scale fleet battles in the Mediterranean Sea remained unchallenged until the Battle of Lepanto in 1571. It was one of the three largest sea battles that took place in the sixteenth century Mediterranean, along with the Battle of Djerba and the Battle of Lepanto.