The prison was activated on June 25, 1944 with the first prisoners arriving soon after. A total of 2,000 inmates were held at the fort over the years, with 560 officers, 576 enlisted men, and 171 civilian employees staffed at the peak of use. Fences that had surrounded the Alien Detention Camp were strengthened and adapted to the area used by the detention camp. Soon after their arrival, inmates proved that the fences were not nearly as secure as they were thought to be when eight inmates escaped from the camp. Over the years many inmates attempted escape, some were wounded, and others were killed during their escape attempts. The disciplinary barracks at Fort Missoula were officially closed on April 18, 1947.
Many of the buildings at Fort Missoula were repurposed during this time. Two buildings still stand from this time period, a set of cellblock buildings built in 1945 and a rec hall and gym that is now used by the US Forest Service. The cellblocks originally had flat roofs and an open courtyard in the middle of each building. The buildings were set for demolition in the 1990’s, but were saved. Today the University of Montana’s Geosciences Department renovated the buildings, one for their use, the other for the University of Montana’s Fine Arts Department.