A critical factor in understanding the development of active continental margins is knowledge of the crustal basement on which magmatic arcs are built. This study reports results from a whole-rock geochemical and zircon U-Pb geochronological study of a suite of crustal xenoliths from the Bolivian Altiplano, Central Andes, that provide new insight into the evolution and composition of the continental basement beneath the region. The xenoliths are hosted in Pliocene–Pleistocene trachyandesitic to dacitic lavas that erupted from monogenetic volcanic centers in the Andean backarc region and comprise both igneous and metamorphic lithologies, including diorites, microgranites, gneisses, garnet–mica schists, granulites, quartzites, and dacites. The xenolith suite exhibits significant Sr-isotopic heterogeneity, with values extending from 0.7105 to 0.7368. Pb isotopic signatures reflect the crustal domains previously constrained from scattered exposures of basement rocks throughout the region. Ion microprobe U-Pb dating of cores and rims from zircon separates from two of the sampled xenoliths reveals predominant early Phanerozoic age peaks (ca. 500 Ma; population 1), late Mesoproterozoic age peaks (1.0–1.2 Ga; population 2), and Paleoproterozoic age peaks (1.7–1.9 Ga; population 3). Populations 1 and 2 are well documented throughout the Andes and correspond to periods of supercontinent formation (e.g., Rodinia at ca. 1.0 Ga) and breakup. Population 3, which is poorly represented in the zircon record of the Andes as a whole, may record geological events during the construction of the Paleoproterozoic Amazonian Craton. The presence of the three age peaks in the detrital zircon population record of a single crustal xenolith demonstrates the important role of crustal recycling in the construction of the modern-day Andean margin. The lithological character of the xenoliths and their detrital zircon ages are inconsistent with current understanding of the eastern extent of the Arequipa-Antofalla basement block beneath the Bolivian Altiplano and instead indicate that it terminates further to the west than previously assumed.