Rapid denudation and uplift of eastern Tibet have accelerated during the Late Miocene due to lateral lower crustal flow, without a significant contribution from upper crustal shortening. However, growing lines of evidence have revealed that Early Cenozoic faulting controlled enhanced denudation and shortening. Here, we report 51 new zircon and apatite (UTh)/He and apatite fission-track ages from seven granite samples along one primary branch fault (the Yunongxi fault) of the Yalong thrust belt in eastern Tibet. Cooling ages and inverse thermal modeling revealed two pulses of accelerated exhumation during the Late Cretaceous (70–65 Ma) and the Late Eocene–Early Oligocene (40–30 Ma). We suspect that the surface uplift of eastern Tibet, due to the convergence rate acceleration between India and Eurasia, triggered the first cooling stage. A synchronous out-of-pace Early Cenozoic cooling pattern across the Yunongxi fault was further identified and could be due to fault initiation at ca. 40–30 Ma. We argue that the Late Eocene–Early Oligocene rapid cooling and exhumation and the associated outward plateau growth were primarily accommodated through upper-crust faulting along the Yalong–Longmen Shan thrust belt. This deformation pulse was the first-stage response of fault activity to the India–Eurasia collision in eastern Tibet. More extensive Late Miocene deformation driven by lateral lower crustal flow consequently bypassed these early-stage fault systems and overwhelmed the Late Cretaceous and Late Eocene–Early Oligocene deformation in eastern Tibet.