Abstract Geomorphic, thermochronologic, geochemical, structural, and geophysical data all lend support to the hypothesis that the Colorado Rocky Mountains are an example of dynamic topography that has responded variably to broad epeirogenic uplift since the late Miocene. Our view is that this epeirogenic uplift is primarily related to mantle buoyancy and to a lesser extent, on isostatic adjustments caused by regional denudation. Neogene uplift components were superimposed on earlier (Laramide and mid-Tertiary) uplift events such that the present-day high topography of the Colorado Rocky Mountains reflects a composite uplift history. Newly recognized gravels of the ancestral Colorado River located beneath lava flows of Grand Mesa suggest that the Colorado River flowed west from the Rocky Mountains out onto the Colorado Plateau by 11 Ma. Radiometric dating of late Miocene basalt flows and thermochronologic data for western Colorado indicate that regional denudation and river incision became much more rapid ca. 9.5–6.0 Ma, prior to integration of the Colorado River through Grand Canyon. Post-10 Ma river incision rates and magnitudes are variable, and we interpret these variations to reflect differential uplift of discrete areas of the Rocky Mountain region during the late Cenozoic. For instance, in areas such as Grand Mesa, the Flat Tops, and the Park Range, incision rates and magnitudes are generally ~100–150 m/m.y. and 1.0–1.5 km, respectively. For comparison, these values are 2–3 times larger than incision rates and magnitudes over the past 5–10 Ma in the upper Green River basin. Differential incision across major structural boundaries indicates that post-10 Ma river incision has been driven by Neogene rock uplift. Additional evidence of post-Laramide deformation includes warping of the Oligocene to early Miocene pre-Browns Park Formation erosion surface. This surface has up to 1.8 km of structural relief that has been produced since the Miocene. For basalt-capped regions such as Grand Mesa and the Flat Tops, Neogene rock uplift of 1.0–1.5 km has probably been accompanied by a commensurate amount of surface uplift, resulting in increased local relief ( England and Molnar, 1990 ). Flexural isostatic modeling suggests that isostatic adjustments account for only 10%–40% of the post-10 Ma rock uplift recorded in western Colorado, and that 850–1500 m of probable post-10 Ma rock uplift cannot be accounted for by the isostatic response to denudation. Areas such as Grand Mesa and the Flat Tops are associated with the largest magnitudes of post-10 Ma rock uplift, and generally overlie areas of anomalously low P-wave velocities (the largest of which is the Aspen Anomaly), which suggests that mantle buoyancy could have driven Neogene uplift of the Colorado Rocky Mountains. 3 He/ 4 He ratios strongly suggest that there are direct mantle-to-surface interactions of neotectonics and surface waters. In summary, we conclude that the Rocky Mountains are continuing to evolve in response to neotectonic events that accelerated in the late Miocene, and which are continuing to drive base-level changes and drainage integration of the modern upper Colorado River system. The combined data are best explained by broad epeirogenic Neogene uplift of the Colorado Rocky Mountains driven by mantle flow and buoyancy.