The valley was the ancestral home of the Salish tribe of the Flathead nation.

In early September 1805, the Lewis and Clark Expedition crossed Lost Trail Pass from present-day Idaho in order to connect with the overland route through the Rocky Mountains. Passing down Camp Creek and the East Fork, they followed the Bitterroot River northward to the point where it connects with the Nez Perce Trail and Lolo Creek. Before continuing their difficult journey to the west, they named their camp Traveler's Rest. Returning to this site in early July of the following year, they split their Corps of Discovery, furthering their explorations both to the northeast (Lewis) and to the south (Clark).

The first 'white' settlement in the valley was the founding in 1841 of St. Mary's Mission, near present-day Stevensville, by Father DeSmet. Fort Owen was established nearby in 1850, and difficult relations occurred between the white settlers and the Salish until 1891, when the native tribes were relocated to the north. In 1877 Chief Joseph and the Nez Perce tribe passed south through the Bitterroot Valley, fleeing the U.S. Army. They exited the East Fork via Gibbons Pass, near where they fought at the Battle of the Big Hole.



The Bitterroot Valley had nearly a million apple trees in the early 1900s, and was one of the world's largest producers of MacIntosh apples at that time. Irrigation was provided by about 80 miles of canals. Although the Bitterroot Valley's orchards became less competitive with apple orchards in Washington State after hailstorms in 1922 and 1923, it is still home to one of the nation's largest cider orchards.

Settlement has continued since that time. The population of Ravalli County in the 2000 census was 36,070; 40,212 in the 2010 census.The major industries are ranching, agriculture, forestry, and tourism.