The founding of Salta took place in the context of Spain's extensive colonization efforts throughout the Americas. Hernando de Lerma, tasked with establishing Spanish control in the region, selected the location for its advantageous positioning near the Salado River, providing essential water resources and fertile land for agriculture. This settlement became crucial for the administration of Spanish territories, as it allowed for better oversight and governance over a large expanse of land inhabited by various indigenous groups. De Lerma's ambition was to foster peaceful relations with the local populations while simultaneously promoting the Spanish Crown's interests.

Following the establishment of Salta, the settlement began to flourish. De Lerma encouraged agriculture and trade, facilitating connections with both local indigenous peoples and other Spanish colonies. Throughout the following years, Salta transformed into a vital center for commerce and agriculture, known for its production of tobacco, fruit, and textiles. Its location also made it an important waypoint for caravans traveling between the highlands and other major urban centers, fostering economic development in the region.

As Salta grew, it became a cultural melting pot where Spanish customs intertwined with indigenous traditions. This fusion would greatly influence the social fabric of the region, paving the way for a distinct local identity. De Lerma's vision for Salta extended beyond mere settlement; he aspired to create a cohesive community within a diverse landscape, contributing to the broader narrative of European colonization in South America.