During Cenozoic time, the Colorado Plateau was raised about 2 km above sea level. The most-recent and best-documented uplift of the plateau (∼1 km) has been concentrated at its southwest margin between 6 and 1 Ma, whereas the eastern Colorado Plateau may have been at high elevations since Eocene time. To better understand the recent tectonic activity at the southwest margin of the Colorado Plateau, we compile detailed crustal thickness and density information from seismic and gravity data for a region that includes northwest Arizona and the southern tip of Nevada. This information is used to isolate the mantle contribution to uplift. We find that there is relatively low density mantle underlying the southern margin of the plateau in northwest Arizona, which could result from about 60–80 km of thinning of the dense mantle lithosphere combined with about 100 °C of heating through a 100-km-thick mantle layer. The available estimates from earthquake-source seismology in or near the study area are compatible with this estimate of lithospheric thinning. We speculate that uplift may result from subduction-related thinning of the continental lithosphere.