By approaching the Civil War from the vantage point of the American West, this article demonstrates how the wartime collapse of civil administrative and economic institutions upended western life and ultimately accelerated the dispossession and conquest of Native lands. Prior to the Civil War, Indigenous people of the upper Missouri River region relied on treaties and trade to manage their relationships with the United States. The Civil War undermined these structures by disrupting transportation networks, accelerating inflation, exacerbating fraud and deliberate mismanagement by Republican officials, and crippling the fur trade. The region’s Native people were plunged into an irreversible state of crisis and found themselves more vulnerable to postwar American empire-building in the 1860s and 1870s. This article builds on previous scholarship connecting the Civil War, the American West, and the Indian wars by emphasizing the profound impact of wartime disruption upon Indigenous communities in the American West.