The site was essentially populated for 8,500 years, within which earthworks structures were built by the Oneota Culture and occupied by descendant tribes such as the Ioway, Otoe, Missouri, and shared with Quapaw and later Kansa, Osage, and Omaha (who were both Omaha and Ponca at the time) people.

[2] The site was substantially looted and areas wholly destroyed by settlers and looters through the late 1930s and by subsequent generations of collectors.

[citation needed] Blood Run was mapped in the early 18th century by French voyageurs trading with the village, which was then populated largely by Omaha people, but other cultures shared the area, about 480 mounds existed and a population of 10,000 Native people was documented in the corresponding census.

The State of South Dakota Game, Fish, and Parks Commission, upon offer of land sale by owners Buzz and Lois Nelson and the sole civilian testimony by SD author of Blood Run (book) (a volume supported by a SD Arts Council Grant) and Sioux Falls Public Schools and Office of Indian Education teacher, Allison Hedge Coke, the Commission voted to acquire the area as state park land in January 2003.

[4] In December 2011, South Dakota Governor Dennis Daugaard announced that an agreement was reached on the purchase option for 324 acres in the Blood Run Historical Landmark area on the Lincoln County, S.D., side of the Big Sioux River.