The population figure for Indigenous peoples in the Americas before the 1492 voyage of Christopher Columbus has proven difficult to establish. Scholars rely on archaeological data and written records from settlers from the Old World. Most scholars writing at the end of the 19th century estimated the pre-Columbian population at about 10 million; by the end of the 20th century the scholarly consensus had shifted to about 50 million, with some arguing for 100 million or more. Contact with the New World led to the European colonization of the Americas, in which millions of immigrants from the Old World eventually settled in the New World.

The population of African and Eurasian peoples in the Americas grew steadily, while the number of the indigenous people plummeted. Eurasian diseases such as smallpox, influenza, bubonic plague and pneumonic plagues devastated the Native Americans who did not have immunity. Conflict and outright warfare with Western European newcomers and other American tribes further reduced populations and disrupted traditional society. The extent and causes of the decline have long been a subject of academic debate, along with its characterization as a genocide.

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