After the United States acquired this area, American Moses Austin renamed the community for the Bolivian silver-mining city of Potosí.

[5] According to the United States Census Bureau, the city has a total area of 2.33 square miles (6.03 km2), all land.

[6] Potosi is located in the Lead Belt region of Missouri; as such, it has mining operations in the area.

It is also geographically considered part of the St. Francois Mountain Range, meaning it has hilly terrain typical of the region.

The city is within proximity to many nature areas, including Mark Twain National Forest and Washington State Park.

Moses obtained a grant of 7,153 arpents of land from the Spanish Empire and started large-scale mining operations, building his town to support it.

Moses named the town after Potosí in Bolivia, which was famous for its vast silver mines.

Another mining entrepreneur in Potosi at the time of Moses Austin was James Bryan.

Firmin Rene Desloge, who emigrated from Nantes, France in 1822 as the progenitor of the Desloge Family in America, settled in Potosi and established a mercantile, distillery, fur trading and lead smelting business.

[11] Potosi is also home to the oldest standing Presbyterian church west of the Mississippi River.

[12] The Potosi Correctional Center, which opened in 1989, housed Missouri's death row until 2005.

The United States Postal Service operates the Potosi Post Office.