The Indigenous peoples of Oklahoma include the Wichita and Caddo, both of which are confederacies of many smaller tribes. They spanned several states. Wichita oral history says that they have been in situ for a million years, and the describe the region as once being covered by a great water (which of course it was in prehuman times).

The earliest known painted object in all of the Americas is the Cooper Bison Skull, a skull of the extinct Bison antiquus with a red zigzag painted on it. It dates back 10K–11K years and was found at at a buffalo kill site on Beaver River in NW Oklahoma and is only display at the Sam Noble Museum in Norman.

Archaeologists have unearthed evidence of Paleoindians throughout the state, but some cultures they describe in particular include: the Calf Creek culture, nomadic hunter-gatherers of Eastern Oklahoma and Western Arkansas, dating back from 5500–2000 BCE. They lived in a particularly arid time and hunted buffalo and antelope. Another hunting-and-gathering society living in southeast Oklahoma is known as the Lawrence culture.

The first evidence of agriculture appears in central and western Oklahoma, dating back possibly 2000 years ago. Maize arrived from Mesoamerica and was a staple of sedentary village life by 800 CE.

The Cooper culture flourished in NE Oklahoma circa 500 CE and had a trade network reaching as far east at present-day St. Louis, Missouri. The Fourche Maline culture lived in the east from 300–800 CE. These ancestral Caddo peoples were part of the Hopewellian exchange, a trade and ideological network that spanned Canada to the Gulf of Mexico. They are known for their Black Midden Mounds.

Spiro Mounds, from 850–1450 CE and in LaFlore County, is Oklahoma's most famous archaeological site. Attributed to ancestral Caddo/Kichai peoples, Spiro was the westernmost major Mississippian center. Maize was the primary staple. Of all the Mississippian sites, Spiro boasts the most elaborate shell-engravings—whelk shell cups used to consumer black drink, a ceremonial beverage containing yaupon holly that is still used today. Copper, wood, pottery, stone, rabbit-fur textiles, and even lace has been recovered from Spiro.

While Caddo cultures flourished in the east, the Panhandle culture, including the Antelope Creek culture, emerged in the west, from 1150 to 1450 CE. They lived on bison, practiced agriculture, mined flint, and built semi-underground, stone-lined pit houses.

Today the federally recognized tribes in Oklahoma are:

Absentee-Shawnee Tribe of Indians
Alabama-Quassarte Tribal Town
Apache Tribe
Caddo Nation of Oklahoma
Cherokee Nation
Cheyenne-Arapaho Tribes
Chickasaw Nation
Choctaw Nation of Oklahoma
Citizen Potawatomi Nation
Comanche Nation
Delaware Nation
Delaware Tribe of Indians
Eastern Shawnee Tribe of Oklahoma
Fort Sill Apache Tribe of Oklahoma
Iowa Tribe of Oklahoma
Kaw Nation
Kialegee Tribal Town
Kickapoo Tribe of Oklahoma
Kiowa Indian Tribe of Oklahoma
Miami Tribe of Oklahoma
Modoc Tribe of Oklahoma
Muscogee (Creek) Nation
Osage Tribe
Ottawa Tribe of Oklahoma
Otoe-Missouria Tribe of Indians
Pawnee Nation of Oklahoma
Peoria Tribe of Indians of Oklahoma
Ponca Tribe of Indians of Oklahoma
Quapaw Tribe of Indians
Sac & Fox Nation
Seminole Nation of Oklahoma
Seneca-Cayuga Tribe of Oklahoma
Shawnee Tribe
Thlopthlocco Tribal Town
Tonkawa Tribe of Indians of Oklahoma
United Keetoowah Band of Cherokee Indians in Oklahoma
Wichita and Affiliated Tribes (Wichita, Keechi, Waco and Tawakonie)
Wyandotte Nation.

The Yuchi and Natchez are not recognized, but Yuchi and Natchez people are enrolled in other federally recognized tribes (mainly Creek, Cherokee, and Shawnee tribes). Oklahoma has 39 tribes. Sometimes it is incorrectly described as having the most tribes of any state; however, California has over 102 federally recognized tribes.