Evidence of early inhabitation comes from a variety of sites and artifacts such as tools, pictographs, stone cairns, scarred trees, tipi rings, hearths, rock quarries, and chipping sites.  Approximately 95 percent of archeological and cultural artifacts in Missoula County have been found along creeks, rivers, and lakes.  Sites of current cultural importance to Native Americans also exist, including undisturbed spiritual sites, prehistoric and historic campsites, burial grounds, and other cultural sites.

For centuries the Missoula Valley offered natural passageways between the mountain ranges, where Native Americans, such as the Salish and Nez Perce, traveled to and from buffalo hunting grounds on the plains east of the Continental Divide.  However, at one location, just west of the confluence of the Big Blackfoot and the Clark Fork Rivers, the narrowing canyon also provided a convenient ambush site, where Blackfeet raiders would attack returning buffalo hunters.  As a result of the bloody confrontations there, the site became known as Hell's Gate, now known as Hellgate Canyon.

The oldest Indian artifacts found in Missoula County date from 12,000 years ago and the first known semi-permanent sites developed 5,500 years ago.  During the following centuries Missoula County was occupied by a succession of Native American tribes.  The introduction of the horse and European settlement in the east resulted in tribal relocations throughout Montana.  By 1700 the Salish, Pend D’Oreille, and Kootenai had been pushed into western Montana by the Blackfeet and other tribes.  The Lolo Trail was used by Nez Perce, Salish and other tribes as a major travel route.  Flathead Lake was a cultural center and a meeting place for nearly all western Montana tribes.  At the time of white settlement, the Missoula County area was used by the Salish, Kootenai, Pend d’Oreille, Blackfeet, and Shoshone tribes.