High topography in central Asia is perhaps the most fundamental expression of the Cenozoic Indo-Asian collision, yet an understanding of the timing and rates of development of the Tibetan Plateau remains elusive. Here we investigate the Cenozoic thermal histories of rocks along the eastern margin of the plateau adjacent to the Sichuan Basin in an effort to determine when the steep topographic escarpment that characterizes this margin developed. Temperature-time paths inferred from 40Ar/39Ar thermochronology of biotite, multiple diffusion domain modeling of alkali feldspar 40Ar release spectra, and (U-Th)/He thermochronology of zircon and apatite imply that rocks at the present-day topographic front of the plateau underwent slow cooling (<1°C/m.y.) from Jurassic times until the late Miocene or early Pliocene. The regional extent and consistency of thermal histories during this time period suggest the presence of a stable thermal structure and imply that regional denudation rates were low (<0.1 mm/yr for nominal continental geotherms). Beginning in the late Miocene or early Pliocene, these samples experienced a pronounced cooling event (>30°–50°C/m.y.) coincident with exhumation from inferred depths of ∼8–10 km, at denudation rates of 1–2 mm/yr. Samples from the interior of the plateau continued to cool relatively slowly during the same time period (∼3°C/m.y.), suggesting limited exhumation (1–2 km). However, these samples record a slight increase in cooling rate (from <1 to ∼3°C/m.y.) at some time during the middle Tertiary; the tectonic significance of this change remains uncertain. Regardless, late Cenozoic denudation in this region appears to have been markedly heterogeneous, with the highest rates of exhumation focused at the topographic front of the plateau margin. We infer that the onset of rapid cooling at the plateau margin reflects the erosional response to the development of regionally significant topographic gradients between the plateau and the stable Sichuan Basin and thus marks the onset of deformation related to the development of the Tibetan Plateau in this region. The present margin of the plateau adjacent to and north of the Sichuan Basin is apparently no older than the late Miocene or early Pliocene (∼5–12 Ma).