The weakness caused by the collapse of Almohad power and the subsequent creation of new Taifas, each with its own ruler, led to the rapid Castile reconquest of the valley of the Guadalquivir. Córdoba was regained in 1236 and Seville in 1248. The fall of Granada on 2 January 1492 put an end to the Nasrid rule, event that marks the beginning of Andalusia, the southern four territories of the Crown of Castile in the Iberian Peninsula.

Seven months later, on 3 August 1492 Christopher Columbus left the town of Palos de la Frontera, Huelva, with the first expedition that resulted in the Discovery of the Americas, that would end the Middle Ages and signal the beginning of modernity. Many Castilians participated in this and other expeditions that followed, some of them known as the Minor or Andalusian Journeys.

Contacts between Spain and the Americas, including royal administration and the shipping trade from Asia and America for over three hundred years, came almost exclusively through the south of Spain, specially Seville and Cadiz ports.

As a result, it became the wealthiest, most influential region in Spain and amongst the most influential in Europe. For example, the Habsburg diverted much of this trade wealth to control its European territories.