The human history of the Americas is thought to begin with people migrating to these areas from Asia during the height of an ice age. These groups are generally believed to have been isolated from the people of the "Old World" until the coming of Europeans in 1492 with the voyages of Christopher Columbus.

The ancestors of today's American Indigenous peoples were the Paleo-Indians; they were hunter-gatherers who migrated into North America. The most popular theory asserts that migrants came to the Americas via Beringia, the land mass now covered by the ocean waters of the Bering Strait. Small lithic stage peoples followed megafauna like bison, mammoth (now extinct), and caribou, thus gaining the modern nickname "big-game hunters." Groups of people may also have traveled into North America on shelf or sheet ice along the northern Pacific coast.

Sedentary societies developed primarily in two regions: Mesoamerica and the Andean civilizations. Mesoamerican cultures include Zapotec, Toltec, Olmec, Maya, Aztec, Mixtec, Totonac, Teotihuacan, Huastec people, Purépecha, Izapa, and Mazatec. Andean cultures include Inca, Caral-Supe, Wari, Tiwanaku, Chimor, Moche, Muisca, Chavin, Paracas, and Nazca.

After the voyages of Christopher Columbus in 1492, Spanish and later Portuguese, English, French and Dutch colonial expeditions arrived in the New World, conquering and settling the discovered lands, which led to a transformation of the cultural and physical landscape in the Americas. Spain colonized most of the Americas from present-day Southwestern United States, Florida and the Caribbean to the southern tip of South America. Portugal settled in what is mostly present-day Brazil while England established colonies on the Eastern coast of the United States, as well as the North Pacific coast and in most of Canada. France settled in Quebec and other parts of Eastern Canada and claimed an area in what is today the central United States. The Netherlands settled New Netherland (administrative centre New Amsterdam – now New York), some Caribbean islands and parts of Northern South America.

European colonization of the Americas led to the rise of new cultures, civilizations and eventually states, which resulted from the fusion of Native American, European, and African traditions, peoples and institutions. The transformation of American cultures through colonization is evident in architecture, religion, gastronomy, the arts and particularly languages, the most widespread being Spanish (376 million speakers), English (348 million) and Portuguese (201 million). The colonial period lasted approximately three centuries, from the early 16th to the early 19th centuries, when Brazil and the larger Hispanic American nations declared independence. The United States obtained independence from Great Britain much earlier, in 1776, while Canada formed a federal dominion in 1867 and received legal independence in 1931. Others remained attached to their European parent state until the end of the 19th century, such as Cuba and Puerto Rico which were linked to Spain until 1899. Smaller territories such as Guyana obtained independence in the mid-20th century, while French Guiana, the Falkland Islands, Bermuda and several Caribbean islands remain part of a European power to this day.

It is believed that the peopling of the Americas began when Paleolithic hunter-gatherers (Paleo-Indians) entered North America from the North Asian Mammoth steppe via the Beringia land bridge, which had formed between northeastern Siberia and western Alaska due to the lowering of sea level during the Last Glacial Maximum (26,000 to 19,000 years ago). These populations expanded south of the Laurentide Ice Sheet, either by sea or land, and spread rapidly southward, occupying both North and South America no later than 14,000 years ago, and possibly before 20,000 years ago. The earliest populations in the Americas, before roughly 10,000 years ago, are known as Paleo-Indians. Indigenous peoples of the Americas have been linked to Siberian populations by the distribution of blood types, and in genetic composition as reflected by molecular data, such as DNA.

While there is general agreement that the Americas were first settled from Asia, the migration patterns and the place(s) of origin in Eurasia of the peoples who migrated to the Americas remain unclear. The most generally accepted theory is that Ancient Beringians moved when sea levels were significantly lowered due to the Quaternary glaciation, following herds of now-extinct Pleistocene megafauna along ice-free corridors that stretched between the Laurentide and Cordilleran ice sheets. Another proposed route has them migrating down the Pacific coast to South America as far as Chile, either on foot or using boats. Any archaeological evidence of coastal occupation during the last Ice Age would now have been covered by the sea level rise, up to a hundred meters since then.

The precise date for the peopling of the Americas is a long-standing open question. While advances in archaeology, Pleistocene geology, physical anthropology, and DNA analysis have progressively shed more light on the subject, significant questions remain unresolved. The Clovis First theory refers to the hypothesis that the Clovis culture represents the earliest human presence in the Americas about 13,000 years ago. Evidence of pre-Clovis cultures has accumulated and pushed back the possible date of the first peopling of the Americas. Academics generally believe that humans reached North America south of the Laurentide Ice Sheet at some point between 15,000 and 20,000 years ago. Current debates center around four glacial-age openings which could have allowed entry into North America: coastal around 24,000 and 15,000 years ago, inland around 14,000 years ago, and coastal around 12,000 years ago. The Swan Point Archaeological Site located in Alaska has yielded the oldest evidence of human habitation that is not disputed, with artifacts that have radiocarbon dates of 14,000 years, indicating the site was occupied around 12,000 BCE.