The Altiplano of southern Peru displays a large spectrum of Cenozoic potassic (K) and ultrapotassic (UK) mafic rocks that delineate two deep lithospheric mantle blocks that have undergone different depletion and enrichment events. Phlogopite lamproites indicate that the eastern Altiplano block is underlain by a metasomatized harzburgitic mantle of Paleoproterozoic to Archean age (depleted mantle age, TDM = 1130–2485 Ma; εNd = −5.0 to −11.4; 87Sr/86Sri = 0.7100–0.7159). Beneath the western Altiplano block, the presence of a younger (TDM = 837–1259 Ma; εNd = +0.6 to −6.3; 87Sr/86Sri = 0.7048–0.7069) metasomatized lherzolitic mantle is deduced from multiple occurrences of diopside-rich K-UK lavas (leucitites, leucite-bearing tephrites, olivine, and diopside trachybasalts). A third suite of young (<2 Ma) K-UK rocks outlines the active Cusco Vilcanota fault system separating the western and eastern Altiplano blocks; this third suite, composed of diopside-phlogopite lamproites and augite kersantites, minettes, and trachybasalts, sampled a composite mantle source that probably included an asthenospheric component (TDM = 612–864 Ma; εNd = −1.1 to −3.5; 87Sr/86Sri = 0.7051–0.7062), in addition to lithospheric components inherited from the eastern and western Altiplano blocks. The spatial distribution of the south Peruvian K-UK magmatism suggests that K-UK melts reached the surface through reuse of older translithospheric weakness zones extending at least to the depth of magma generation. These latter were reactivated by a dextral transpressional regime imposed on the two rigid lithospheric blocks by the Andean orogen.