Don Francisco Fernández de la Cueva was born in Barcelona into one of the most aristocratic families of Spain, as the eldest surviving son from the third marriage of his father, Francisco Fernández de la Cueva, 7th Duke of Alburquerque (1575–1637).

His father was "one of the toughest, most rigorous, and successful of the viceroys of Catalonia...and had specialized in the [sic] suppression of disorder.

In his 3rd marriage, the Duke married Ana Enríquez de Cabrera y Colonna and had 9 children; his wife survived him some 21 years.

Because of this he strengthened the defenses of Veracruz and San Juan de Ulúa on the east coast of New Spain.

He increased trade with the Philippines, Siam and Cochinchina, sending mercury, saltpeter and other mineral products.

He ordered the resumption of the minting of gold coins (suspended by Viceroy Antonio de Mendoza).

The viceroy accelerated the construction of the new cathedral of Mexico City, visiting it every afternoon, climbing the scaffolding, and giving monetary rewards to the workers.

Justice was swift for his attacker, who was quickly tried, then dragged around the city and back to the Plaza Mayor, where he was hanged the next day.