Viceroyalty of Peru replaces New Castile Governorate
Exploration and settlement (1542–1643)
In 1542, the Spanish organized the existing governorates into the Viceroyalty of New Castile, which shortly afterward would be called the Viceroyalty of Peru, in order to properly control and govern the Spanish South America.
In 1544, Holy Roman Emperor Charles V (King Charles I of Spain) named Blasco Núñez Vela Peru's first viceroy. From September 2, 1564, to November 26, 1569, Lope García de Castro, a Spanish colonial administrator who constituted the first Audiencia in Spanish South America, served as the interim viceroy of Peru.
Although established, the viceroyalty was not properly organized until the arrival of Viceroy Francisco Álvarez de Toledo, who made an extensive tour of inspection of the region. Francisco de Toledo, "one of the great administrators of human times", established the Inquisition in the viceroyalty and promulgated laws that applied to Indians and Spanish alike, breaking the power of the encomenderos and reducing the old system of mita (the Incan system of mandatory labor tribute). He improved the defensibility of the viceroyalty with fortifications, bridges, and la Armada del Mar del Sur (the Southern Fleet) against pirates. He ended the indigenous Neo-Inca State in Vilcabamba, executing the Inca Túpac Amaru, and promoted economic development from the commercial monopoly and mineral extraction, mainly from silver mines in Potosí.
The Amazon Basin and some large adjoining regions had been considered Spanish territory since the Treaty of Tordesillas and explorations such as that by Francisco de Orellana, but Portugal fell under Spanish control between 1580 and 1640. During this time, Portuguese territories in Brazil were controlled by the Spanish crown, which did  object to the spread of Portuguese settlement into parts of the Amazon Basin that the treaty had awarded to Spain. Still, Luis Jerónimo de Cabrera, 4th Count of Chinchón sent out a third expedition to explore the Amazon River, under Cristóbal de Acuña; this was part of the return leg of the expedition of Pedro Teixeira.
Some Pacific islands and archipelagoes were visited by Spanish ships in the sixteenth century, but they made no effort to trade with or colonize them. These included New Guinea (by Ýñigo Ortiz de Retez in 1545), the Solomon Islands (in 1568), and the Marquesas Islands (in 1595) by Álvaro de Mendaña de Neira.