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The syntaxes at the eastern and western ends of the Himalaya located in the Tsangpo and Indus gorge regions provide examples of the interplay between tectonics and erosion. A previous borehole study along the Yarlung River in the Eastern Himalayan Syntaxis (EHS) revealed an ∼1 km thick sedimentary wedge upstream of the Tsangpo gorge with a >2.5 Ma depositional age. However, the mechanism of formation of this sedimentary wedge remains under debate. Here, we combine low-temperature thermochronology data and thermomechanical modelling to discuss how a sedimentary wedge formed at the highly eroded EHS. Our low-temperature thermochronology results show late Miocene fast cooling episodes focused at the Gyaca and Tsangpo gorges, which are interpreted to be related to coeval rifting at the former and rapid erosion and hot-crust upwelling at the latter. Constrained by the geological and geophysical observations, we apply thermomechanical models to illustrate the mechanism of formation of the sedimentary wedge and present high relief of the EHS. The numerical geodynamic model shows that localized erosion triggers middle 'crust extrusion' and regional topographic adjustment at the EHS. Supplementary material: Supplementary figures and tables are available at https://doi.org/10.6084/m9.figshare.c.7008098 Thematic collection: This article is part of the Mesozoic and Cenozoic tectonics, landscape and climate change collection available at: https://www.lyellcollection.org/topic/collections/mesozoic-and-cenozoic-tectonics-landscape-and-climate-change [ABSTRACT FROM AUTHOR]