From the time of the Lewis and Clark Expedition to the mid-century point, few other white men visited the Missoula Valley. The notable exceptions were explorers such as David Thompson and the Jesuit missionaries who came to the Bitterroot Valley in 1841 to establish St. Mary's Mission, near present day Stevensville.
In 1855, Isaac Stevens, Governor of Washington Territory, met with the Chiefs of the Salish, Pend d’Oreille, and Kootenai Tribes at Council Grove along the Clark Fork River near Missoula to negotiate a treaty. Under the terms of the Hellgate Treaty, the Kootenai and Pend d’Oreilles would move to the Flathead Reservation in the Jocko Valley, while the Bitterroot Salish would remain in the Bitterroot Valley.
The treaty stated that no portion of the Bitterroot Valley south of Lolo Creek would be opened to settlement until the area had been surveyed. Although the government did not conduct surveys, white settlers moved into the valley. In 1871, Salish subchiefs Arlee and Joseph agreed to move to the Flathead Reservation, but Chief Charlo refused. He and several hundred followers remained in the Bitterroot Valley until 1891 when, facing starvation, they were removed under military escort.
Between 1859 and 1863, Captain John Mullan supervised construction of a military road between Fort Walla Walla, Washington, and Fort Benton, Montana. Mullan's road reached the Missoula Valley in 1860. The road became a thoroughfare for thousands of travelers to gold rush sites, as well as for settlers heading to the Missoula Valley and other locations throughout the West. Prospectors following Mullan Road into Missoula County discovered gold at Garnet-Coloma, Elk Creek, Ninemile, Lolo Creek, and other areas.
Captain C.P. Higgins and Francis L. Worden, a Walla Walla merchant, established the first settlement in the Missoula area in 1860 at the Hellgate Trading Post located about four miles west of the existing townsite. It and Missoula Mills, established in 1864 at the present townsite, were built on the Mullan Road to trade with the Indians, with those traveling to the region's mines, and with the ranchers and farmers who began to settle in the adjoining valleys. Trading posts were often constructed where tribes came together to meet.
In the summer of 1877, the U.S. Army constructed Fort Missoula, which became a source of economic stability for the town between the end of the placer mining era and the coming of the railroad. The Bonner, Hammond, and Eddy Company (later the Missoula Mercantile) established in 1866, dominated the wholesale and retail trade in the region by the 1880’s and made Missoula the largest trade center within a 75-mile radius.
The construction of the Northern Pacific Railroad through Missoula in 1883, converted it from a town of 300 in 1880 to a city of 12,000 in 1920, with an economy based on trade, timber, and agriculture. In 1886, A.B. Hammond built what was reputed to have been the world's largest lumber mill at Bonner, seven miles east of Missoula. The mill produced timbers for railroad structures and the Butte-area mines, and lumber for building construction.
Agriculture attracted thousands to the area in the early 1900's with the opening of the Flathead Indian Reservation, the promotion of homesteading, and the construction of the Chicago, Milwaukee, St. Paul and Pacific Railroad through Missoula. Large irrigation projects were constructed in the Bitterroot and Flathead Valleys, which became famous for their orchards.