[12] Piyale Pasha received his formal education at the Enderun School (Imperial Academy) in Constantinople (modern-day Istanbul), Ottoman Empire.

The following year Sultan Suleiman the Magnificent assigned him with the task of helping France against the Spaniards upon request by Catherine de' Medici, mother of King Francis II, and Piyale Pasha set sail on 26 June 1555.

In June 1558, joined by Turgut Reis, Piyale Pasha sailed to the Strait of Messina and the two admirals captured Reggio Calabria.

This caused fear throughout the Mediterranean coasts of Spain, and King Philip II appealed to Pope Paul IV and his allies in Europe to bring an end to the rising Ottoman threat.

Giovanni Andrea Doria managed to escape with a small vessel, but the surviving Christians, now under the command of Álvaro de Sande, took refuge in the fort on the island of Djerba which they had constructed during the expedition.

He later landed on Abruzzo, Molise, and Apulia in Italy and captured several strategic fortresses, including Francavilla al Mare,[13] Ortona on August 10,[14] but failing to take Pescara[15] In 1568 he was promoted to Vizier, becoming the first admiral in Ottoman history to reach this rank.

The Ottomans managed to rebuild a fleet as large as that lost at Lepanto in less than a year, and Uluç Ali Reis reconquered Tunisia from Spain and their Hafsid vassals in 1574.