Early in his mandate in New Spain, he sent Captain Diego Martínez de Hurdaide to suppress an uprising of the Tehuecos, an ethnic subgroup of the Cahuitas of Sinaloa.
He established a tribunal to regulate the buying, selling and taxing of mercury metal used in gold and silver metallurgy, which the mines of New Spain had begun to produce in some quantity at Huancavelica.
In Peru, Fernández de Córdoba reformed the fiscal system and stopped the inter-family rivalry that was bloodying the domain, mainly in the fabulous silver city of Potosí, between vicuñas and vascongados.
In 1624 he fortified Lima against pirate attacks, including those by Jacques l'Hermite, a Flemish merchant, explorer and admiral known for his journey around the globe with the Nassau Fleet (1623–1626) and for his blockade and raid on Callao in 1624 during that same voyage in which he also died.
In 1629, Viceroy Diego Fernández de Córdoba gave up his charge and returned to Spain, where he died the following year, at Guadalcázar, aged 52.