Spanish America refers to the Spanish territories in the Americas during the Spanish colonization of the Americas. The term "Spanish America" was specifically used during the territories' imperial era between 15th and 19th centuries. To the end of its imperial rule, Spain called its overseas possessions in the Americas and the Philippines "The Indies", an enduring remnant of Columbus's notion that he had reached Asia by sailing west. When these territories reach a high level of importance, the crown established the Council of the Indies in 1524, following the conquest of the Aztec Empire, asserting permanent royal control over its possessions. Regions with dense indigenous populations and sources of mineral wealth attracting Spanish settlers became colonial centers, while those without such resources were peripheral to crown interest. Once regions incorporated into the empire and their importance assessed, overseas possessions came under stronger or weaker crown control.

The crown learned its lesson with the rule of Christopher Columbus and his heirs in the Caribbean, and they never subsequently gave authorization of sweeping powers to explorers and conquerors. The Catholic Monarchs' conquest of Granada in 1492 and their expulsion of the Jews "were militant expressions of religious statehood at the moment of the beginning of the American colonization." The crown's power in the religious sphere was absolute in its overseas possessions through the papacy's grant of the Patronato real, and "Catholicism was indissolubly linked with royal authority." Church-State relations were established in the conquest era and remained stable until the end of the Habsburg era in 1700, when the Bourbon monarchs implemented major reforms and changed the relationship between crown and altar.

The crown's administration of its overseas empire was implemented by royal officials in both the civil and religious spheres, often with overlapping jurisdictions. The crown could administer the empire in the Indies by using native elites as intermediaries with the large indigenous populations. Administrative costs of empire were kept low, with a small number of Spanish officials generally paid low salaries. Crown policy to maintain a closed commercial system limited to one port in Spain and only a few in the Indies was in practice not closed, with European merchant houses supplying Spanish merchants in the Spanish port of Seville with high quality textiles and other manufactured goods that Spain itself could not supply. Much of the silver of the Indies was diverted into those European merchant houses. Crown officials in the Indies enabled the creation of a whole commercial system in which they could coerce native populations to participate while reaping profits themselves in cooperation with merchants.

The Spanish conquest was facilitated by the spread of diseases such as smallpox, common in Europe but never present in the New World, which reduced the indigenous populations in the Americas. This sometimes caused a labor shortage for plantations and public works and so the colonists informally and gradually, at first, initiated the Atlantic slave trade.

One of the most accomplished conquistadors was Hernán Cortés, who, leading a relatively small Spanish force but with local translators and the crucial support of thousands of native allies, achieved the Spanish conquest of the Aztec Empire in the campaigns of 1519–1521. This territory later became the Viceroyalty of New Spain, present day Mexico. Of equal importance was the Spanish conquest of the Inca Empire by Francisco Pizarro, which would become the Viceroyalty of Peru. The Spanish conquest of the Maya began in 1524, but the Maya kingdoms resisted integration into the Spanish Empire with such tenacity that their defeat took almost two centuries.

After the conquest of Mexico, rumors of golden cities (Quivira and Cíbola in North America and El Dorado in South America) motivated several other expeditions. Many of those returned without having found their goal, or finding it much less valuable than was hoped. Indeed, the New World colonies only began to yield a substantial part of the Crown's revenues with the establishment of mines such as that of Potosí (Bolivia) and Zacatecas (Mexico) both started in 1546. By the late 16th century, silver from the Americas accounted for one-fifth of Spain's total budget.

Eventually the world's stock of precious metal was doubled or even tripled by silver from the Americas. Official records indicate that at least 75% of the silver was taken across the Atlantic to Spain and no more than 25% across the Pacific to China. Some modern researchers argue that due to rampant smuggling about 50% went to China. In the 16th century "perhaps 240,000 Europeans" entered American ports.

Further Spanish settlements were progressively established in the New World: New Granada in the 1530s (later in the Viceroyalty of New Granada in 1717 and present day Colombia), Lima in 1535 as the capital of the Viceroyalty of Peru, Buenos Aires in 1536 (later in the Viceroyalty of the Río de la Plata in 1776), and Santiago in 1541.