In November 1848, John C. Fremont hired Williams to guide his ill-fated fourth expedition through the Southern Rocky Mountains.[4] Fremont sought to find a railroad route through the Rockies along the 38th parallel north. Williams warned Fremont against following his intended route through the La Garita Mountains in winter, but Fremont proceeded with his 35 men and 150 mules. The expedition eventually became hopelessly mired in deep snow and 11 men and all but a few of the pack animals died.[5] Williams led a rescue party south towards Taos, and the survivors of the expedition eventually managed to follow.[6]
In March, Williams and Dr. Benjamin Kern returned to the La Garita Mountains in hopes of finding more survivors. On March 14, 1849, Ute warriors murdered Bill Williams and Dr. Kern in the mountains by for trespassing on Ute lands.[4]