During and after the European colonization of the Americas, European settlers practiced widespread enslavement of Indigenous peoples. In the 15th century, the Spanish introduced chattel slavery through warfare and the cooption of existing systems. A number of other European powers followed suit, and from the 15th through the 19th centuries, between two and five million Indigenous people were enslaved, which had a devastating impact on many Indigenous societies, contributing to the overwhelming population decline of Indigenous peoples in the Americas.

After the decolonization of the Americas, the enslavement of Indigenous peoples continued into the 19th century in frontier regions of some countries, notably parts of Brazil, Peru Northern Mexico, and the Southwestern United States. Some Indigenous groups adopted European-style chattel slavery during the colonial period, most notably the "Five Civilized Tribes" in the United States, however far more Indigenous groups were involved in the selling of Indigenous slaves to Europeans.

Colonial period

European enslavement of Indigenous Americans began with the Spanish colonization of the Caribbean. In Christopher Columbus's letter to Queen Isabella and King Ferdinand of Spain describing the Native Taíno, he remarks that "They ought to make good and skilled servants"Robert H. Fuson, ed., The Log of Christopher Columbus, Tab Books, 1992, International Marine Publishing, . and "these people are very simple in war-like matters... I could conquer the whole of them with 50 men, and govern them as I pleased".Columbus (1991, p. 87). Or "these people are very simple as regards the use of arms ... for with fifty men they can all be subjugated and made to do what is required of them." (Columbus & Toscanelli, 2010, p. 41) The Catholic Monarchs initially rejected Columbus' enthusiasm for the slave trade. But although they issued a decree in 1500 that specifically forbade the enslavement of Indigenous people, they allowed three exceptions which were freely abused by colonial Spanish authorities: slaves taken in "just wars"; those purchased from other Indigenous people; or those from groups alleged to practice cannibalism (such as the Kalinago). Prior to Spain's prohibition on enslaving Indigenous peoples of the Americas, Columbus brought Indigenous slaves back to Spain with him on his return journeys from the Caribbean.

As other European colonial powers joined the Spanish, the practice of Indigenous enslavement was expanded. The new international market for products like tobacco, sugar, and raw materials incentivized the creation of extraction- and plantation-based economies in eastern North America, such as English Carolina, Spanish Florida, and (Lower) French Louisiana. At first, slave labor for these colonies was obtained largely by trading with neighboring tribes, such as the Yamasee. This trade in slaves was new: prior to the arrival of Europeans, tribes in eastern North America did not view slaves as commodities that could be bought and sold freely. Anthropologist David Graeber argued that debt and the threat of violence made this sort of transformation of human beings into commodities possible. Tribes like the Yamasee raided for slaves in order to pay back the debt they owed to European traders for finished goods. This in turn created a demand for guns and ammunition, which further indebted the slave-raiding tribes and created a vicious cycle. Most (but not all) tribes in eastern North America had not considered the status of slave heritable, and often integrated the children of slaves into their own communities. The export of slaves to European colonies (and the high death rates there) created an unprecedented population drain. Slave-raiding also led to constant wars between tribes, and eventually destroyed or threatened to destroy most peoples in the vicinity of the colonies. By the mid eighteenth century, population decline, frequent rebellions, and the availability of African slaves had caused a shift away from the large-scale enslavement of Indigenous peoples. Although it would be continued on the frontiers, in the economic cores of settler societies Indigenous slaves would be replaced with those of African origin.

Spanish colonies

By 1499, Spanish settlers on Hispaniola had discovered gold in the Cordillera Central. This created a demand for large amounts of cheap labor, and an estimated 400,000 Taíno people from across the island were soon enslaved to work in gold mines. As discussed above, this practice of enslaving native peoples was immediately but ineffectually opposed by the Spanish Crown. Succeeding governors were appointed and recalled, often because of stories about their treatment of native populations.Noble, David Cook. "Nicolás de Ovando" in Encyclopedia of Latin American History and Culture, vol. 4, p. 254. New York: Charles Scribner's Sons 1996. The Taíno people also resisted fiercely and were put down in a series of brutal massacres. Nonetheless, forced labor continued and was institutionalized as the encomienda system during the first decade of the 16th century.Ida Altman, et al., The Early History of Greater Mexico, Pearson, 2003, p. 47 Under this system, private Spanish colonizers (encomenderos) were granted the right to the labor of groups of non-Christian Indigenous people. Although based on similar grants given during the Reconquista in Spain, in the Caribbean the system quickly became indistinguishable from the slavery it replaced. By 1508, the original Taíno population of 400,000 or more had been reduced to around 60,000. Spanish slave-raiding parties travelled across the Caribbean and "carried off entire populations" to work their colonies. Although disease is often pointed to as the cause of this population decline, the first recorded smallpox outbreak in the New World was not until 1518. Historian Andrés Reséndez at the University of California, Davis asserts that even though disease was a factor, the Indigenous population of Hispaniola would have rebounded the same way Europeans did following the Black Death if it were not for the constant enslavement they were subject to. He says that "among these human factors, slavery was the major killer" of Hispaniola's population, and that "between 1492 and 1550, a nexus of slavery, overwork and famine killed more natives in the Caribbean than smallpox, influenza or malaria." By 1521, the islands of the northern Caribbean were largely depopulated.

Members of the Spanish religious and legal professions were especially vocal in opposing the enslavement of native peoples. The first speech in the Americas for the universality of human rights and against the abuses of slavery was given on Hispaniola, a mere nineteen years after the first contact. Resistance to Indigenous captivity in the Spanish colonies produced the first modern debates over the legitimacy of slavery. Friar Bartolomé de Las Casas, author of A Short Account of the Destruction of the Indies, publicized the conditions of Indigenous Americans and lobbied Charles V to guarantee their rights. The Spanish progressively restricted and outright forbade the enslavement of Indigenous Americans in the early years of the Spanish Empire with the Laws of Burgos of 1512 and the New Laws of 1542. The latter replaced the encomienda with the repartimiento system, making the Indigenous people (in theory) free vassals of the Spanish Crown. Under repartimiento, Amerindians were paid wages for their work, but the work was still obligatory and still carried out under the supervision of a Spanish conquistador. Legally, these labor obligations were not allowed to interfere with the Amerindians' own survival, with only 7–10% of the adult male population allowed to be assigned to work at any time. The implementation of the New Laws and liberation of tens of thousands of Indigenous Americans led to a number of rebellions and conspiracies by encomenderos which were put down by the Spanish crown. Las Casas' writings gave rise to Spanish Black Legend, which Charles Gibson describes as "the accumulated tradition of propaganda and Hispanophobia according to which the Spanish Empire is regarded as cruel, bigoted, degenerate, exploitative and self-righteous in excess of reality". In later centuries, this would be used by other colonial powers to justify their own treatment of native populations as being at least superior to the Spanish alternative.

Despite being technically illegal, Indigenous slavery continued in Spanish America for centuries after the promulgation of the New Laws. Even in Spain itself, the use of Indigenous slaves did not end until the early 1600s. "Spanish masters resorted to slight changes in terminology, gray areas, and subtle reinterpretations to continue to hold Indians in bondage." Viceroys of New Spain justified enslaving large groups of natives by classifying wars of conquest (such as the Mixtón and Chichimeca Wars) as rebellions.Philip Wayne Powell, quoted in "The Indigenous People of Zacatecas " by John P. Schmal. Retrieved Dec 23, 2010 Franciscan missions abused their grant of ten years' labor from surrounding peoples as grounds for perpetual servitude.Beasley, Delilah L. (1918). "Slavery in California," The Journal of Negro History, Vol. 3, No. 1. (Jan.), pp. 33–44. Slavery was a major cause of the Pueblo Revolt of 1680 and other unrest among the Indigenous people of northern Mexico. Following the revolt, the business of providing enslaved people for the New Mexico market passed into the hands of the Navajo, Utes, Comanches, and Apaches. When the market for slaves began to dry up in the early 18th century, the surplus and ex-slaves settled in New Mexico, forming communities of so-called Genízaros. In 1672, Mariana of Austria freed the enslaved Indigenous people of Mexico. On 12 June 1679, Charles II issued a general declaration freeing all Indigenous slaves in Spanish America. In 1680 this was included in the Recopilación de las leyes de Indias, a codification of the laws of Spanish America. The Kalinago, "cannibals," were the only exception. The royal anti-slavery crusade did not end the enslavement of Indigenous people in Spain's American possessions, but, in addition to resulting in the freeing of thousands of enslaved people, it ended the involvement and facilitation by government officials of enslaving by the Spanish; purchase of slaves remained possible but only from Indigenous enslavers such as the Kalina or the Comanches.

In the Viceroyalty of Peru, the repartimiento system was particularly harsh. The colonial government repurposed the Inca mit'a system under their own administration. For over two centuries, thirteen thousand mitayos were forcefully conscripted every year to work in the silver mines of Potosí, Caylloma, and Huancavelica. Mitayos were forced to carry backbreaking loads in extreme conditions from the depths of the mine up to the surface.Bakewell, 130. Falls, accidents, and illnesses (including mercury poisoning from the refinement process) were all commonplace. To avoid the repartimiento, thousands fled their traditional villages and forfeited their ayllu land rights. From the 16th to late 17th centuries, Upper Peru lost nearly 50% of its Indigenous population. This only increased the burden on the remaining natives, and by the 1600s, up to half of the eligible male population (as opposed to the repartimiento's original 7–10%) might find themselves working at Potosí in any given year. Laborers were paid, but the pay was dismal: just the cost of traveling to Potosí and back could be more than a mitayo was paid in a year, and so many of them chose to remain in Potosí as wage workers when their service was finished.Bakewell, 125.