The Rocky Mountains and adjacent western Great Plains share a common history of late Cenozoic stream incision. Both epeirogenic uplift and climate change (with no associated uplift) have been proposed as the cause of this subcontinental-scale erosional episode. However, the lack of a well-defined Cenozoic paleoelevation history for the region has hampered our ability to distinguish between the two. A tilt analysis of the Cheyenne Tablelands in the western Great Plains of Wyoming and Nebraska provides us with a datum from which postdepositional changes in slope can be determined. Miocene to earliest Pliocene gravels of the Ogallala Group (17.5–5 Ma) cap the tablelands, which currently tilt down to the east at slopes as great as 10−2. However, paleohydraulic analysis of the Ogallala gravels indicates depositional slopes of 10−3 to 10−4, implying a postdepositional increase in tilt. If a hinge point at the eastern edge of the Cheyenne Tablelands is assumed, this tilt translates into differential uplift of 680 m (815–410 m) at the western edge of the Great Plains. Flexural isostatic rebound of the tablelands due to known young erosion in surrounding basins only produces a few hundred meters of uplift. Therefore, even if all of the recent erosion in the region can be attributed to climate change, the resulting rebound is insufficient to account for the observed uplift of the tablelands. Thus, the tilting of the Cheyenne Tablelands is most consistent with broad- wavelength tectonic uplift centered under the Rocky Mountains initiated during Ogallala deposition and continuing since deposition ceased.