Before Columbus’s arrival, the Americas were inhabited by thousands of groups of indigenous peoples, each with distinct cultures and languages. Their patterns of life varied widely, from hunter-gatherer tribes organized into tribal confederations on the North American plains to the large-scale agriculture-based empires of the Mexica and the Inca. Although historians continue to debate the numbers, the best estimate is that in 1492 the peoples of the Americas numbered around 50 million.

Their lives were radically transformed by the arrival of Europeans. In the sixteenth century, perhaps two hundred thousand Spaniards immigrated to the New World. After assisting in the conquest of the Mexica and the Incas, these men carved out vast estates called haciendas in temperate grazing areas and imported Spanish livestock. In coastal tropical areas, the Spanish erected huge plantations to supply sugar to the European market. Around 1550, silver was discovered in present-day Bolivia and Mexico. To work the cattle ranches, sugar plantations, and silver mines, the conquistadors first turned to the indigenous peoples.

The Spanish quickly established the encomienda system, in which the Crown granted the conquerors the right to employ groups of Native Americans as laborers or to demand tribute from them in exchange for providing food and shelter. Theoretically, the Spanish were supposed to care for the indigenous people under their command and teach them Christianity; in actuality, the system was a brutal form of exploitation only one level removed from slavery.

The new conditions and hardships imposed by conquest and colonization resulted in enormous native population losses. The major cause of death was disease. Having little or no resistance to diseases brought from the Old World, the inhabitants of the New World fell victim to smallpox, typhus, influenza, and other illnesses. Another factor was overwork, from which native workers died in staggering numbers. Forced labor diverted local people from agricultural work, leading to malnutrition, reduced fertility rates, and starvation. Malnutrition and hunger in turn lowered resistance to disease. Many indigenous peoples also died through outright violence in warfare.5

The Franciscan Bartolomé de Las Casas (1474–1566) was one of the most outspoken critics of Spanish brutality against indigenous peoples. Las Casas and other missionaries asserted that the Indians had human rights, and through their persistent pressure, the Spanish emperor Charles V abolished the worst abuses of the encomienda system in 1531.

Franciscan, Dominican, and Jesuit missionaries who accompanied the conquistadors and other European settlers played an important role in converting indigenous peoples to Christianity, teaching them European methods of agriculture, and instilling loyalty to their colonial masters. In areas with small Spanish populations, the friars set up missions for a period of ten years, after which established churches and priests would take over and they could move on to new areas. Jesuits in New France also established missions far distant from the centers of French settlement.

Missionaries’ success in conversion varied over time and space. In Central and South America, large-scale conversion forged enduring Catholic cultures in Portuguese and Spanish colonies. Galvanized by their opposition to Catholicism and fueled by their own religious fervor, English colonizers also made efforts to convert indigenous peoples. On the whole, however, these attempts were less successful, in part because the English did not establish wholesale dominance over large native populations as did the Spanish.

Rather than a straightforward imposition of Christianity, conversion entailed a complex process of cultural exchange. Catholic friars were among the first Europeans to seek understanding of native cultures and languages as part of their effort to render Christianity comprehensible to indigenous people. In turn, Christian ideas and practices in the New World took on a distinctive character.

The pattern of devastating disease and population loss occurred everywhere Europeans settled. The best estimate of native population loss is a decline from roughly 50 million people in 1492 to around 9 million by 1700. It is important to note, however, that native populations and cultures did survive the conquest period, sometimes by blending with European incomers and sometimes by maintaining cultural autonomy.

For colonial administrators, the main problem posed by the astronomically high death rate was the loss of a subjugated labor force to work the mines and sugar plantations. As early as 1511, King Ferdinand of Spain observed that the Indians seemed to be “very frail” and that “one black could do the work of four Indians.”6 Thus was born an absurd myth, and the new tragedy of the transatlantic slave trade would soon follow (see "Sugar and Slavery").