Since the late 1990s thousands of new Border Patrol agents, hundreds of miles of fencing, and additional immigration checkpoints have been added to the Mexico-U.S. border region. This unprecedented increase in boundary enforcement has strained existing relationships and created new separations between people and places in the borderlands. Southwestern Arizona has been impacted in especially dramatic ways, as the “hardening” of the international boundary has transformed conservation and indigenous spaces into theaters of drug interdiction and immigration control. This dissertation explores this transformation in southwestern Arizona, a region that was known by Spanish Colonial administrators as the Papaguería. With the community of Ajo at the center of the narrative, this dissertation explores the ways that industry and conservation have long shaped the social relations and the landscape of the region. The destruction of old borders, the creation of new borders, and the redefinition of space has been an ongoing process that continues to define some groups of people as insiders and other groups as outsiders. In the current era of border security echoes from earlier colonial encounters reverberate into the present, shaping landscapes and the lives of local residents in the contemporary Papaguería in significant ways.