He and an older brother, Pedro, migrated to the Viceroyalty of Perú in 1538, and following his enlistment in the Spanish Army, Jerónimo was eventually made a sergeant and stationed in the colonial nerve center of Cuzco, in 1549.

He led numerous military campaigns in subsequent years, notably among them the suppression of revolts in Ica and Nazca, and following a post in the capital, Lima, he was appointed in 1571 corregidor of Potosí.

An initial settlement, Quisquisacate, failed within days of its 24 June 1573 establishment, and on 6 July the expedition chose a location on the banks of the Suquía River, around 250 mi (400 km) south of Santiago de Estero.

He departed towards the east on his own initiative in 1574 and quickly reached the shores of the Paraná River, over 200 mi (320 km) away, establishing the Fort of San Luis (near what today is Santa Fe, Argentina).

Founding the Viceroyalty of Perú's first viable beach-head towards the Atlantic Ocean (via the highly-navigable Paraná), the feat met with the rivalry of Captain Juan de Garay, who had been sent down the river from Asunción with orders from the Viceroy to do the same.