He was part of the relief expedition that saved Gonzalo Pizarro, who was under siege in Cochabamba, and between 1538 and 1539 he participated in the conquest of the province of Charcas, in present-day Bolivia, under the command of Diego de Rojas.

When he heard that Pedro de Valdivia was on his way to conquer Chile in 1540, he moved his troops (composed of 15 horsemen and 10 foot soldiers) to Tarapacá, where he waited for two months in order to join him.

[2] Aguirre quickly became a close confidant of Valdivia and achieved a premier place in the new colony, being named one of the Alcaldes of the first settlement of Santiago and being severely injured in the defense of the city on 11 September 1541, when local Indians led by Michimalonco destroyed it.

On 20 June 1549 Aguirre was appointed lieutenant governor of the zone between the Atacama Desert and the Choapa River, charged with the reconstruction of La Serena, which had been destroyed by Indians from the north.

In 1552 the Lieutenant General of La Serena, Aguirre took possession of Tucumán, on the other side of the Andes, after disputing the claim of Juan Núñez de Prado, who did not recognize the authority of Valdivia.

The conflict was finally resolved when a petition was sent to the Audiencia in Lima,[4] which determined that the council had to submit to the command for six months, after which the viceroy Andrés Hurtado de Mendoza, 3rd Marquis of Cañete would designate a new governor.