 In the face of this threat Pope Paul succeeded in February 1538 in organizing the "Holy League" which consisted of the Papal States, the Republic of Venice, the Maltese Knights and Spain with her vassal states of Naples and Sicily.To confront Barbarossa and his roughly 120 galleys and fustas, the League assembled a fleet of about 300 ships (162 galleys and 140 sailing ships) in September 1538 near Corfu.Its supreme commander was the Genoese admiral Andrea Doria, who was then in the service of Emperor Charles V.

The two fleets met on 28 September 1538 in the Battle of Preveza, and Barbarossa decisively defeated the numerically superior Christian alliance.