The Grand Canyon region provides an excellent laboratory to examine the interplay between river incision, magmatism, and the geomorphic and tectonic processes that shape landscapes. Here we apply U-series, Ar–Ar, and cosmogenic burial dating of river terraces to examine spatial variations in incision rates along the 445 km length of the Colorado River through Grand Canyon. We also analyze strath terrace sequences that extend to heights of several hundred meters above the river, and integrate these with speleothem constrained maximum incision rates in several reaches to examine any temporal incision variations at the million-year time frame. This new high-resolution geochronology shows temporally steady long-term incision in any given reach of Grand Canyon but significant variations along its length from 160 m/Ma in the east to 101 m/Ma in the west. Spatial and temporal patterns of incision, and the long timescale of steady incision rule out models where geomorphic controls such as climate oscillations, bedrock strength, sediment load effects, or isostatic response to differential denudation are the first order drivers of canyon incision. The incision pattern is best explained by a model of Neogene and ongoing epeirogenic uplift due to an eastward propagating zone of increased upper mantle buoyancy that we infer from propagation of Neogene basaltic volcanism and a strong lateral gradient in modern upper mantle seismic structure.