The Pre-Columbian era incorporates all period subdivisions in the history and prehistory of the Americas before the appearance of significant European influences on the American continents, spanning the time of the original settlement in the Upper Paleolithic period to European colonization during the Early Modern period.

While the phrase "pre-Columbian era" literally refers only to the time preceding Christopher Columbus's voyages of 1492, in practice the phrase is usually used to denote the entire history of indigenous Americas cultures until those cultures were vanquished, diminished, or extensively altered by Europeans, even if this happened decades or centuries after Columbus's first landing.

However, much as many people around the world may possibly know of the existence of Native  Americans, little has been discussed about the ethnic cleansing that Christopher Columbus brought about with the discovery of America and the fate which Native Americans faced. The truth of the ethnic cleansing which took place back in the 15th century has been placed under the carpet for hundreds of years and the decline in Native American population is often covered up by attributing it to the epidemic outbreak of smallpox, typhus, measles, influenza, bubonic plague, cholera, malaria, tuberculosis, mumps, yellow fever and pertussis. Hence, this research will delve deeper into the ugly truth of American history and seek to learn of the other truths for the decline in Native Americans.

While epidemic disease was a leading factor of the population decline of the American indigenous peoples after 1492, there were other contributing factors, all of them related to European contact and colonization. One of these factors was warfare. According to demographer Russell Thornton, although many lives were lost in wars over the centuries, and war sometimes contributed to the near extinction of certain tribes, warfare and death by other violent means was a comparatively minor cause of overall native population decline.

From the U.S. Bureau of the Census in 1894: "The Indian wars under the government of the United States have been more than 40 in number. They have cost the lives of about 19,000 white men, women and children, including those killed in individual combats, and the lives of about 30,000 Indians. The actual number of killed and wounded Indians must be very much higher than the given... Fifty percent additional would be a safe estimate..."

There is some disagreement among scholars about how widespread warfare was in pre-Columbian America, but there is general agreement that war became deadlier after the arrival of the Europeans and their firearms. Europeans had gunpowder and swords, which made killing easier and war more deadly. Europeans proved consistently successful in achieving domination in warfare with Native Americans for a variety of reasons. One reason was the staying power of the Europeans, who could call on a far ranging supply network, and could sustain a conflict over several years including the winters if necessary. Almost no Indian tribe had the stored resources to conduct a war for more than a few months. European colonization also contributed to a number of wars between Native Americans, who fought over which of them should have first access to the new weapon.

Some Spaniards objected to the encomienda system, notably Bartolomé de las Casas, who insisted that the Indians were humans with souls and rights. Due to many revolts and military encounters, Emperor Charles V helped relieve the strain on both the Indian laborers and the Spanish vanguards probing the Caribana for military and diplomatic purposes. Later on New Laws were promulgated in Spain in 1542 to protect isolated natives, but the abuses in the Americas were never entirely or permanently abolished. The Spanish also employed the pre-Columbian draft system called the mita, and treated their subjects as something between slaves and serfs. Serfs stayed to work the land; slaves were exported to the mines, where large numbers of them died. In other areas the Spaniards replaced the ruling Aztecs and Incas and divided the conquered lands among themselves ruling as the new feudal lords with often, but unsuccessful lobbying to the viceroys of the Spanish crown to pay Tlaxcalan war demnities. The infamous Bandeirantes from São Paulo, adventurers mostly of mixed Portuguese and native ancestry, penetrated steadily westward in their search for Indian slaves. Serfdom existed as such in parts of Latin America well into the 19th century, past independence.

Friar Bartolomé de las Casas and Antonius Flávio Chesta (Tony Chesta) and other dissenting Spaniards from the colonial period described the manner in which the natives were treated by colonials. This has helped to create an image of the Spanish conquistadores as cruel in the extreme.

Great revenues were drawn from Hispaniola so the advent of losing manpower didn't benefit the Spanish crown. At best, the reinforcement of vanguards sent by the Council of the Indies to explore the Caribana country and gather information on alliances or hostilities was the main goal of the local viceroys and their adelantados. Although mass killings and were not a significant factor in native depopulation, no mainstream scholar dismisses the sometimes humiliating circumstances now believed to be precipitated by civil disorder as well as Spanish cruelty.

Even more consequential than warfare or mistreatment on indigenous populations was the geographic displacement of Native American tribes. The increased European population due to immigration and high birth rates of Native European settlers put pressure on native tribes to relocate and alter their traditional ways of life. Displacement of native peoples living traditionally often resulted in increased infant mortality and often higher death rates which steadily lowered their populations for some time. In the United States, for example, the relocation of Native Americans resulting from the policies of Indian removal and the reservation system created a disruption which resulted in fewer live births and a short term population decline.

The populations of many Native American peoples were reduced by the common practice of intermarrying with Europeans. Although many Indian cultures that once thrived are extinct today, their descendants exist today in some of the bloodlines of the current inhabitants of the Americas.