He was the third son of Íñigo López de Mendoza y Quiñones, 1st Marquis of Mondéjar and Francesca Pacheco.

He returned to sea with six galleys, but was recalled to La Goleta to prevent the unpaid and mutinous Spanish garrison from selling the fortress to the Turks.

In 1540, Mendoza gained an important victory in the Battle of Alborán, crushing superior Turkish forces.

In 1555, he was temporarily Viceroy of Naples because Cardinal Pedro Pacheco de Villena attended the Papal conclave, May 1555.

Very uncomfortable at court, Mendoza soon left for Flanders to fight under Emmanuel Philibert, Duke of Savoy against the French.