The generation and evolution of continental topography are fundamental geologic and geomorphic concerns. In particular, the history of landscape development might contain useful information about the spatiotemporal evolution of deep Earth processes, such as mantle convection. A significant challenge is to generate observations and theoretical predictions of sufficient fidelity to enable landscape evolution to be constrained at scales of interest. Here, we combine substantial inventories of stratigraphic and geomorphic observations with inverse and forward modeling approaches to determine how the North American landscape evolved. First, stratigraphic markers are used to estimate postdepositional regional uplift. Present‐day elevations of these deposits demonstrate that >2 km of long‐wavelength surface uplift centered on the Colorado‐Rocky‐Mountain plateaus occurred in Cenozoic times. Second, to bridge the gaps between these measurements, an inverse modeling scheme is used to calculate the smoothest spatiotemporal pattern of rock uplift rate that yields the smallest misfit between 4,161 observed and calculated longitudinal river profiles. Our results suggest that Cenozoic regional uplift occurred in a series of stages, in agreement with independent stratigraphic observations. Finally, a landscape evolution model driven by this calculated rock uplift history is used to determine drainage patterns, denudation, and sedimentary flux from Late Cretaceous times until the present day. These patterns are broadly consistent with stratigraphic and thermochronologic observations. We conclude that a calibrated inverse modeling strategy can be used to reliably extract the temporal and spatial evolution of the North American landscape at geodynamically useful scales.