The desire of the Mormon settlements for economic self-sufficiency led to mining by missionaries for lead. In 1856 Nathaniel V. Jones was sent to recover ore from the "Mountain of Lead" 30 miles southwest of the mission at Las Vegas Springs. About 9,000 pounds were recovered before smelting difficulties forced the remote mine to be abandoned in 1857. Potosi became the first abandoned mine in Nevada.

In 1861 California mining interests reopened the mine, and a smelter and rock cabins of 100 busy miners made up the mining camp of Potosi. Even more extensive operations resulted after the transcontinental Salt Lake and San Pedro R.R. (now Union Pacific) was built through the county in 1905.

During World W ar I, Potosi was an important source of zinc.