In the easternmost Himalaya and southeastern Tibet, the Namche Barwa–Gyala Peri massif and adjacent Lhasa block host some of the Earth’s most active geologic processes and extreme topography. Synthesis of U-Th/He and Ar-Ar thermochronology, anatectic history, seismicity, and structural geology shows the important role that surface processes have played in this region in both local and orogen-scale crustal dynamics. Basement rocks of the massif underwent an episode of metamorphism, partial melting, and focused deformation that began ca. 10 Ma and likely remains active due to thermally mediated feedbacks between these processes and erosion. Strong differential rock uplift at Namche Barwa established the immense Namche Barwa knickzone on the Yarlung Tsangpo River, which has been stabilized through coupling between erosion driven by high stream power and localized deformation. This knickzone has maintained a high secondary base level of ~3000 m for the upper Yarlung Tsangpo watershed and so has shielded a large region of southeastern Tibet from excavation by the river, which in turn could alter the morphology and so the dynamics of the eastern Himalayan orogenic wedge. The landscape evolution of the southeast Lhasa block involved slow regional unroofing or incision in the Neogene, a significant pulse of ~5 km of rapid exhumation from ca. 10 to 5 Ma, and since then a great reduction in exhumation started once the Namche Barwa knickzone on the Yarlung Tsangpo was established. The low-relief high-elevation surface in the area is a relatively young feature, developed after the rapid 10–5 Ma exhumation pulse.