Trappers and a Franciscan explorer/priest, Francisco Garces experienced what is now Nevada. But John C. Fremont probably made the first methodical observations of the area from 1843-1845. In 1841 West Coast-bound settlers began crossing the Humboldt Valley and the Forty Mile Desert, a route followed later by the Overland State Lines. Concluding the Mexican War, The Treaty of Guadalupe Hidalgo on February 2, 1848, granted to the United States territory that included Nevada.

The Mormons founded the first permanent settlement at Genoa in the Carson Valley in 1849 and a mission at Las Vegas Valley in 1853. Monthly mail service across northern Nevada began in 1853. The Pony Express crossed central Nevada beginning in 1860, and the telegraph began through the area in 1861.