Late Cenozoic volcanic rocks erupted in the southern Salar de Uyuni region of the central Andes provide evidence for recent modification of both the lower and upper continental crust during subduction-zone magmatism. At a given SiO2 content, K2O and related incompatible trace element concentrations increase eastward in basaltic andesite samples and are associated with increasing Sr isotopic ratios and decreasing Sr concentrations. These data favor a model in which basaltic andesite magmas are contaminated by lower continental crust that becomes increasingly more mafic toward the active volcanic front because of relatively recent intrusion and hybridization by primary basaltic magmas. Compositions of andesitic lavas continue the geochemical trends established by the basaltic andesite samples except that Sr isotopic ratios of lavas erupted at the arc front are constant to slightly decreasing with increasing SiO2 contents. Assimilation of upper-crustal rocks that also vary in composition across the strike of the arc is the most plausible mechanism to produce the distinct Sr isotopic trends of the andesitic lavas. At the volcanic front, the magmas producing the andesitic lavas assimilated rocks within the Quaternary volcanic and plutonic complex of the Andean arc itself. Toward the east, the magmas assimilated basement rocks that become progressively older with distance from the volcanic front because of diminishing modification by late Cenozoic arc magmatism. Thus, the across-arc geochemical trends in the southern Salar de Uyuni region are consequences of spatial variations in the composition of the lower and upper continental crust, and these variations appear to be linked to the subduction process itself.