His mother was Catalina de Mendoza, daughter of the Count of Monteagudo.
In 1555, he became commander of the Spanish land and sea in the relief of the Turkish siege of Oran and Bugía.
He led the Spanish troops during the early stages of the Morisco Revolt together with Luis Fajardo, 2nd Marquis of los Vélez.
The American historian Henry Charles Lea wrote of Mondéjar's "short but brilliant campaign...
The Moriscos speedily lost heart and sought terms of surrender… By the middle of February [1569] the rebellion was practically suppressed.