Jedidiah Smith used the Mojave Indian Trail to cross the Mojave Desert in 1826. Though tribe members first welcomed the trappers, conflict was not long in coming.

In 1827, another trapping party came through Mojave land, ignoring the tribe’s requests for goods in exchange for trapped animals. The resultant conflict left victims on both sides. When Smith returned later that year, his party was also attacked, and for the next 20 years violence reigned, reaching a peak when trappers from the Hudson Bay Company killed 26 Mojaves.

Joseph Reddeford Walker, in 1834 had crossed the northern portions of the Mojave and into the Great Basin Desert searching for a route to Salt Lake city. Traveling through California, Walker and his party saw redwood forests, experienced a major earthquake, and witnessed a meteor shower. Returning east, Walker went down to the southern end of the San Joaquin Valley and traveled through what would become known as Walker's Pass, which, years later was to be one of the main gateways for gold-seekers migrating into California.

The Mojave Indian Trail was used by Kit Carson when he was guide for Captain John Fremont in 1844. Fremont recorded the geology and types of plants as well as making maps of the geography of the region.

The Old Spanish Trail came into the Mojave Desert from the north. It was used as a trade route from Santa Fe to Los Angeles. The two trails met at the Mojave River.