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Paleo-Indians were the first peoples who entered and subsequently inhabited the Americas towards the end of the Late Pleistocene period. The prefix paleo- comes from the Ancient Greek adjective: παλαιός, romanized: palaiós, lit. ' old; ancient '. The term Paleo-Indians applies specifically to the lithic period in the Western Hemisphere and is distinct from the term Paleolithic.

Traditional theories suggest that big-animal hunters crossed the Bering Strait from North Asia into the Americas over a land bridge (Beringia). This bridge existed from 45,000 to 12,000 BCE (47,000–14,000 BP). Small isolated groups of hunter-gatherers migrated alongside herds of large herbivores far into Alaska. From c. 16,500 – c. 13,500 BCE (c. 18,500 – c. 15,500 BP), ice-free corridors developed along the Pacific coast and valleys of North America. This allowed land animals, followed by humans, to migrate south into the interior of the continent. The people went on foot or used boats along the coastline. The dates and routes of the peopling of the Americas remain subjects of ongoing debate. It is likely there were three waves of ancient settlers from the Bering Sea to the America continent.

Stone tools, particularly projectile points and scrapers, are the primary evidence of the earliest human activity in the Americas. Archeologists and anthropologists use surviving crafted lithic flaked tools to classify cultural periods. Scientific evidence links Indigenous Americans to eastern Siberian populations by the distribution of blood types, and genetic composition as indicated by molecular data, such as DNA. There is evidence for at least two separate migrations.

Paleoindians lived alongside and hunted many now extinct megafauna (large animals), with most large animals across the Americas becoming extinct towards the end of the Paleoindian period as part of the Late Pleistocene megafauna extinctions. The potential role of human hunting in the extinctions has been the subject of much controversy.

From 8000 to 7000 BCE (10,000–9,000 BP) the climate stabilized, leading to a rise in population and lithic technology advances, resulting in a more sedentary lifestyle during the following Archaic Period.