In 1527, Sebastián Caboto established Fort Sancti Spiritu on the Paraná River, the first European settlement in what is now Argentina. Its destruction in 1529 showed how hard it would be to hold the river corridor without stable supplies and alliances. The episode also kept Spanish interest focused on the region’s waterways and rumors of inland wealth.
In August 1535, Pedro de Mendoza led a major expedition from Spain to establish a permanent foothold at the Río de la Plata. The goal was to secure Spanish control of the estuary and open a base for movement into the interior along the Paraná–Paraguay river system. This expedition set the stage for both early failures and later, more durable colonial towns.
On 1536-02-02, Mendoza’s expedition founded a settlement at the Río de la Plata later known as Buenos Aires. It was intended as a strategic port and a starting point for expansion up-river. Shortages and conflict with local Indigenous groups soon undermined the settlement’s survival.
In 1536, Juan de Ayolas moved up the Paraná River and founded the fort called Corpus Christi to support exploration and resupply. River forts like this were meant to protect communications and help the Spanish push inland. The shift upriver also reflected how difficult it was to keep the coastal settlement supplied.
By about 1537, Juan de Ayolas’ attempt to reach and raid inland areas ended when his party was killed after returning downriver. The loss removed an important leader and weakened Spanish plans for rapid conquest beyond the river corridor. It also increased pressure on surviving settlements to consolidate rather than keep pushing deeper into contested territory.
On 1537-08-15, Juan de Salazar de Espinosa established a fort named Nuestra Señora de la Asunción. Over time, it became the main Spanish base in the region because it was easier to sustain and defend than the exposed coastal camp. Asunción would later support further expeditions and new town foundations downstream.
In August 1538, surviving conquistadors elected Domingo Martínez de Irala as captain general under emergency conditions. This reflected both the isolation of the colony and the lack of clear leadership after earlier setbacks. Irala’s authority helped organize a regional retreat toward the stronger upriver base at Asunción.
Between 1539 and 1541, Irala began transferring the remaining people from Buenos Aires to Asunción. The move was a practical decision: the coastal settlement struggled with supplies and security, while Asunción had become the more sustainable center. This relocation shifted Spanish power away from the estuary and upriver into Paraguay.
On 1540-03-18, Álvar Núñez Cabeza de Vaca was appointed adelantado (a royal governor with conquest and settlement authority) for the Río de la Plata region. The appointment signaled the Crown’s intent to reassert control and redirect expansion after earlier failures. It also set up a political struggle with local leaders who had gained power during the crisis years.
By 1541, the first Buenos Aires settlement was deliberately depopulated and abandoned, with survivors sent to Asunción. The failure showed that controlling the Río de la Plata estuary required stronger logistics and more settlers than the first expedition could sustain. For decades afterward, Asunción served as the main base for Spanish expansion in the region.
In 1542, Cabeza de Vaca reached Asunción by an overland route from coastal Brazil, using Indigenous trails. His arrival aimed to stabilize the colony and push exploration toward Andean wealth. However, the difficult journey and strained relations with colonists and rivals limited his long-term effectiveness.
On 1544-04-25, a rebellion in the colony deposed Cabeza de Vaca and restored Irala’s faction to power. The episode revealed how weak royal authority could be at long distance, especially when local leaders controlled supplies and manpower. Political instability slowed broader plans for downstream resettlement at the Río de la Plata.
On 1573-11-15, Juan de Garay founded Santa Fe de Vera Cruz on the Paraná River. The new town was meant to serve as a mid-river link between Asunción and the Atlantic, strengthening Spanish communications and trade. Santa Fe became a key step toward reoccupying the Río de la Plata coastline with a stronger, better-supported effort.
Conquest of the Río de la Plata and foundation of the Río de la Plata colonies (1535–1573)