The pathway, in combination with the river, made the area a stopping place for Native Americans and later explorers, including the Mountain Men. With the advent of travel to Oregon, California, and Utah, it also became a stop for wagon trains on this part of the Oregon/California/Utah trial. The Donner party encamped here on July 24, 1846 having made its fateful decision to try a new shortcut to California beyond Fort Bridger. Seven miles east of here, on June 28, 1847, the first Mormon wagon train with the Prophet Brigham Young met with frontiersman Jim Bridger on the Little Sandy River. The next day, the Mormons rested at the Big Sandy before pushing on to reach the Green River that same day.

By 1858, the Big Sandy Mail Station had developed as a site for mail service between the Missouri River and Salt Lake City. The Central Overland California & Pike's Peak Express Company, which operated the Pony Express, made the mail station one of the original stops for its famed Pony Express and Overland Stage service. The Pony Express started on April 3, 1860 and operated 19 ½ months, only to be replaced by the Transcontinental Telegraph service whose telegraph line came through at this location.

Other notable travelers like Horace Greeley, Sir Richard Burton, Samuel Clemens (Mark Twain), and tens of thousands of trail emigrants used this pathway traveling either East or West, but mainly West.

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