The Spanish conquistadores, who were primarily poor nobles from the impoverished west and south of Spain, began building up an American empire in the Caribbean, using islands such as Cuba, Puerto Rico, and Hispaniola as bases. Florida fell to Juan Ponce de León after 1513. From 1519 to 1521, Hernán Cortés waged a campaign against the Aztec Empire, ruled by Moctezuma II. From the territories of the Aztec Empire conquistadors expanded Spanish rule to northern Central America and parts of what is now southern and western United States. Other conquistadors took over the Inca Empire after crossing the Isthmus of Panama and sailing the Pacific to northern Peru. As Francisco Pizarrosubdued the empire in a manner similar to Cortés other conquistadores used Peru as base for conquering much of Ecuador and Chile. In Colombia, Bolivia, and Argentina conquistadors from Peru linked up with other conquistadors arriving more directly from the Caribbean and Río de la Plata-Paraguay respectively. Conquistadors founded numerous cities many of them on locations with pre-existing pre-colonial settlements including the capitals of most Latin American countries.
Besides conquest Spanish conquistadors made significant explorations into the Amazon Jungle, Patagonia, the interior of North America, and the Pacific Ocean.
Portugal established a route to China in the early 16th century, sending ships via the southern coast of Africa and founding numerous coastal enclaves along the route. Following the discovery in 1492 by Europeans of the New World with Christopher Columbus's first voyage there and the first circumnavigation of the world by Juan Sebastián Elcano in 1521 (both voyages promoted by the Spanish Crown of Castile), expeditions led by conquistadors in the 16th century established trading routes linking Europe with all these areas.