Continental topography is the result of complex interactions among mantle convection, continental dynamics, and climatic and erosional processes. Therefore, topographic evolution of mountain belts and continental interiors reflects directly upon the coupling between mantle and surface processes. It has recently been proposed that the modern topography of western North America is partly controlled by the removal of the subducting Farallon plate and replacement of lithospheric mantle by hot asthenosphere, creating surface uplift of the Colorado Plateau, the southwestern United States, and northern Mexico, while concomitant subsidence characterizes the central United States. How the topography of the Cenozoic North American Cordillera evolved in the past is largely unknown, yet currently debated tectonic models each have a predictable topographic response. Here we examine Cenozoic surface uplift patterns of western North America based on a record of ∼3000 stable isotope proxy data. This data set is consistent with Eocene north to south surface uplift in the Cordillera, culminating in the assembly of an Eocene–Oligocene highland 3–4 km in elevation. The diachronous record of surface uplift and associated magmatism further supports tectonic models calling for the convective removal of mantle lithosphere or removal of the Farallon slab by buckling along an east-west axis. The Eocene–Oligocene development of rainout patterns similar to present-day patterns along the flanks of the Cordilleran orogen is therefore unlikely to be the result of late Mesozoic crustal thickening and associated development of an Andean-style Altiplano.