In an unsuccessful attempt to control the crossing of the Colorado River and carry out missionary work among the Indians of southeastern Utah, forty-one men were called by Mormon leaders in April 1855 to establish the Elk Mountain Mission at present-day Moab. Traveling from Sanpete Valley along the Old Spanish Trail, the group crossed the Colorado River in mid-June and commenced construction of a rock fort. They remained until late September of 1855, at which time they returned to Sanpete Valley after Indian attacks destroyed their crops and left three men dead.

More than two decades later, in 1878, permanent settlers returned to Moab to establish farms and ranches. As the community evolved, a Mormon ward and a community school were established in 1881. Construction of the Denver and Rio Grande Western Railroad between Denver and Salt Lake City brought the railroad to within thirty-five miles of Moab at Thompson Springs and provided a much-desired railroad connection.

A ferry across the Colorado River was in operation by 1885. The first bridge across the Colorado, a three-span steel bridge, was completed in 1912. By the first decade of the twentieth century, Moab had developed as one of Utah's finest fruit-growing areas, producing peaches, apples, and some grapes. Moab became the county seat when Grand County was created from portions of Emery and Uintah counties in 1890. Moab was incorporated as a town in January 1903 and became a third-class city in December 1936.