Tunupa volcano is a composite cone in the central Andean arc of South America located ∼115 km behind the arc front. We present new geochemical data and 40Ar/39Ar age determinations from Tunupa volcano and the nearby Huayrana lavas, and we discuss their petrogenesis within the context of the lithospheric dynamics and orogenic volcanism of the southern Altiplano region (∼18.5°S–21°S). The Tunupa edifice was constructed between 1.55 ± 0.01 and 1.40 ± 0.04 Ma, and the lavas exhibit typical subduction signatures with positive large ion lithophile element (LILE) and negative high field strength element (HFSE) anomalies. Relative to composite centers of the frontal arc, the Tunupa lavas are enriched in HFSEs, particularly Nb, Ta, and Ti. Nb-Ta-Ti enrichments are also observed in Pliocene and younger monogenetic lavas in the Altiplano Basin to the east of Tunupa, as well as in rear arc lavas elsewhere on the central Andean Plateau. Nb concentrations show very little variation with silica content or other indices of differentiation at Tunupa and most other central Andean composite centers. We propose that this distinct compositional domain reflects an amphibole- and/or phlogopite-rich mantle lithospheric source. Breakdown of these minerals during lithospheric delamination may provide a melting trigger for Tunupa, as has been suggested for other rear arc plateau lavas of the central Andes, and for plateau regions globally. The ca. 11 Ma Huayrana lavas indicate that this process had begun in the central Altiplano Basin by this time. The enriched Nb-Ta-Ti signature of plateau lavas may be an important indicator of hydrous mineral breakdown within the mantle lithosphere, and it can be detected in lavas that that have likely experienced crustal contamination.