The post also protected the nearby routes of the Union Pacific Railroad and the Oregon-California Trail, providing a safe haven for travelers. Though the pioneers may have seen it as an oasis on the frontier, its officers and troops did not, considering it a hardship post due to its lack of adequate supplies and equipment, which had to be hauled in from Fort Laramie.

Not withstanding its remote location and frequent desertions by enlisted men, the fort continued to grow and develop and by 1870 it was well established. A number of well-known old west personalities such as Jim Bridger, Wild Bill Hickok, Calamity Jane and "Buffalo Bill" Cody who were among the many whose some of those travels frequently took them to the fort. It became the base for General George Crook’s three expeditions in 1876 into the Powder River area: in March, culminating in the Battle of Powder River, Montana; in May-June, ending in the Battle of the Rosebud, also in Montana; and in November, highlighted by the defeat of Dull Knife's Cheyennes along the Powder River.

The latter expedition, combined with others in 1876-77, ended the major Indian Wars with the northern Plains tribes. With the Indians confined to reservations, the fort outlived its usefulness and Fort Fetterman was abandoned in 1882.