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Estimates of how many people were living in the Americas when Columbus arrived have varied tremendously; 20th century scholarly estimates ranged from a low of 8.4 million to a high of 112.5 million persons. Given the fragmentary nature of the evidence, precise pre-Columbian population figures are impossible to obtain, and estimates are often produced by extrapolation from comparatively small bits of data.

In 1976, geographer William Denevan used these various estimates to derive a "consensus count" of about 54 million people, although some recent estimates are lower than that.
On an estimate of approximately 50 million people in 1492 (including 25 million in the Aztec Empire and 12 million in the Inca Empire), the lowest estimates give a death toll of 80% at the end of the 16th century (8 million people in 1650).
Latin America would only reattain this level at the turn of the 20th century, with 17 million in 1800; 30 million in 1850; 61 million in 1900;105 million in 1930;218 million in 1960; 361 million in 1980, and 563 million in 2005.
In the last thirty years of the 16th century, the Mexican population highly decreased to attain the low level of one million people in 1600.

The Maya population is today estimated at 6 million, which is the same level as at the end of the 15th century.In what is now Brazil, the indigenous population has declined from a pre-Columbian high of an estimated 4 million to some 300,000.

Historian David Henige has argued that many population figures are the result of arbitrary formulas selectively applied to numbers from unreliable historical sources, a deficiency he sees as being unrecognized by several contributors to the field. He believes there is not enough solid evidence to produce population numbers that have any real meaning, and characterizes the modern trend of high estimates as "pseudo-scientific number-crunching." Henige does not advocate a low population estimate; rather, he argues that the scanty and unreliable nature of the evidence renders broad estimates suspect, and that "high counters" (as he calls them) have been particularly flagrant in their misuse of sources.[3] Although Henige's criticisms are directed against some specific instances, other studies do generally acknowledge the inherent difficulties in producing reliable statistics given the almost complete lack of any hard data for the period in question.

This population debate has often had ideological underpinnings. Low estimates were sometimes reflective of European notions of their own cultural and racial superiority, as historian Francis Jennings has argued: "Scholarly wisdom long held that Indians were so inferior in mind and works that they could not possibly have created or sustained large populations." At the other end of the spectrum, some have argued that contemporary estimates of a high pre-Columbian indigenous population are rooted in a bias against aspects of Western civilization and/or Christianity. Robert Royal writes that "estimates of pre-Columbian population figures have become heavily politicized with scholars who are particularly critical of Europe often favoring wildly higher figures."

Since civilizations rose and fell in the Americas before Columbus arrived, the indigenous population in 1492 was not necessarily at a high point, and may have already been in decline. And Fernand Braudel has pointed out a problem that the Amerindian faced that was not a factor on other continents: "The Indian population ... suffered from a demographic weakness, particularly because of the absence of any substitute animal milk. Mothers had to nurse their children until they were three or four years old. This long period of breast-feeding severely reduced female fertility and made any demographic revival precarious." Indigenous populations in most areas of the Americas reached a low point by the early twentieth century, and in a number of cases started to climb again.In the United States, the numbers may have already recovered to pre-Columbian levels.