Bioarchaeological approaches are well suited for examining past responses to political and environmental changes. In the Andes, we hypothesized that political and environmental changes around AD 1100 resulted in behavioral changes, visible as shifts in paleodiet and paleomobility, among individuals in the San Pedro de Atacama oases and Loa River Valley. To investigate this hypothesis, we generated carbon and oxygen isotope data from cemeteries dating to the early Middle Horizon (Larache, Quitor-5, Solor-3), late Middle Horizon (Casa Parroquial, Coyo Oriental, Coyo-3, Solcor-Plaza, Solcor-3, Tchecar), and Late Intermediate Period (Caspana, Quitor-6 Tardio, Toconce, Yaye-1, Yaye-2, Yaye-3, Yaye-4). Carbon isotope data demonstrate a greater range of carbon sources during the late Middle Horizon compared with the Late Intermediate Period; while most individuals consumed largely C-3 sources, some late Middle Horizon individuals consumed more C-4 sources. Oxygen isotope data demonstrate greater diversity in drinking water sources during the late Middle Horizon compared with the Late Intermediate Period. Water samples were analyzed to provide baseline data on oxygen isotope variability within the Atacama Desert, and demonstrated that oxygen isotope values are indistinguishable in the San Pedro and Loa Rivers. However, oxygen isotope values in water sources in the high-altitude altiplano and coast are distinct from those in the San Pedro and Loa Rivers. In conclusion, instead of utilizing a wider variety of resources after environmental and political changes, individuals exhibited a wider range of paleodietary and paleomobility strategies during the Middle Horizon, a period of environmental and political stability. Am J Phys Anthropol 157:179-201, 2015. (c) 2015 Wiley Periodicals, Inc.