It was for many years the largest trading post in the northern Great Plains and a major trans-shipment point for buffalo furs.

It served as a midpoint among the outposts of the American Fur Company (AFC), which monopolized trade on the upper Missouri by 1830, and as an endpoint for a major overland shipment route to Fort Laramie in present-day eastern Wyoming.

[3] The first people of European descent to encounter Native Americans in the Fort Pierre area were a pair of French explorers, the La Vérendrye brothers, during their 1743–44 expedition.

They buried an inscribed lead plate on a hill near the confluence of the Missouri and Bad Rivers, claiming the territory for the King as part of New France.

When Chouteau ascended the Missouri River in 1832 on the maiden voyage of the steamship Yellowstone, he ordered construction of what was formally dubbed Fort Pierre in his honor.

In addition to its central location for company logistics, it was also generally surrounded by a settlement of Lakota Sioux and other Plains Indian tribes, who traded buffalo furs for American and European goods.

At its height in the 1850s, the company was part of a complex trading network extending from the Rocky Mountains to the Eastern United States and Europe: it shipped 100,000 fur robes through Fort Pierre.

Salvageable buildings and materials were transported to Fort Randall, and any surviving timbers were used to fuel steamboats on the river.

The trade in buffalo furs effectively ended by the early 1860s, when the United States Army established a presence in the region.