The Colorado plateau is a large, tectonically intact, physiographic province in the southwestern North American Cordillera that stands at similar to 1,800-2,000 m elevation and has long been thought to be in isostatic equilibrium(1). The origin of these high elevations is unclear because unlike the surrounding provinces, which have undergone significant Cretaceous-Palaeogene compressional deformation followed by Neogene extensional deformation, the Colorado plateau is largely internally undeformed. Here we combine new seismic tomography(2) and receiver function images to resolve a vertical high-seismic-velocity anomaly beneath the west-central plateau that extends more than 200 km in depth. The upper surface of this anomaly is seismically defined by a dipping interface extending from the lower crust to depths of 70-90 km. The base of the continental crust above the anomaly has a similar shape, with an elevated Moho. We interpret these seismic structures as a continuing regional, delamination-style foundering of lower crust and continental lithosphere. This implies that Pliocene (2.6-5.3 Myr ago) uplift of the plateau and the magmatism on its margins are intimately tied to continuing deep lithospheric processes. Petrologic and geochemical observations indicate that late Cretaceous-Palaeogene (similar to 90-40 Myr ago) low-angle subduction hydrated and probably weakened much of the Proterozoic tecto-spheric mantle(3-5) beneath the Colorado plateau. We suggest that mid-Cenozoic (similar to 35-25 Myr ago) to Recent magmatic infiltration subsequently imparted negative compositional buoyancy to the base and sides of the Colorado plateau upper mantle, triggering downwelling. The patterns of magmatic activity suggest that previous such events have progressively removed the Colorado plateau lithosphere inward from its margins(6), and have driven uplift. Using Grand Canyon incision rates(7,8) and Pliocene basaltic volcanism patterns, we suggest that this particular event has been active over the past similar to 6 Myr.