We use inverse models of mantle convection to explore the vertical evolution of the Colorado Plateau. By satisfying multiple constraints (seismic tomography, stratigraphy in the western United States and Great Plains, and other structural and volcanic data adjacent to the plateau), the model provides predictions on the continuous history of Colorado Plateau vertical motion since 100 Ma. With the arrival of the flat-lying Farallon slab, dynamic subsidence swept from west to east over the plateau and reached a maximum ca. 86 Ma. Two stages of uplift followed the removal of the Farallon slab below the plateau: one in the latest Cretaceous and the other in the Eocene with a cumulative uplift of ∼1.2 km. Both the descent of the slab and buoyant upwellings raised the plateau to its current elevation during the Oligocene. A locally thick plateau lithosphere enhances the coupling to the upper mantle so that the plateau has a higher topography with sharp edges. The models predict that the plateau tilted downward to the northeast before the Oligocene, caused by northeast-trending subduction of the Farallon slab, and that this northeast tilting diminished and reversed to the southwest during the Miocene in response to buoyant upwellings.