The eastern termination of the Himalayan orogen forms a structural syntaxis that is characterised by young (from 10 to < 1 Ma) mineral growth and cooling ages that document Late Miocene to Pleistocene structural, metamorphic, igneous and exhumation events. This region is a steep antiformal and in part domal structure that folds the suture zone between the Indian and Asian plates. It is dissected by the Yarlung Tsangpo, one of the major rivers of the eastern Himalayan–Tibet region, which becomes the Brahmaputra River in the Indian foreland basin before emptying into the Bay of Bengal. Exceptionally high relief and one of the deepest gorges on Earth have developed where the river's tortuous route crosses the Namche Barwa–Gyala Peri massif (> 7 km in elevation) in the core of the syntaxis. Very high erosion rates documented in sediment downstream of the gorge at the foot of the Himalaya contribute ~ 50% of total detritus to the sediment load of the Brahmaputra. The initiation of very high rates of exhumation has been attributed either to the extreme erosive power of a river flowing across a deforming indentor corner and the associated positive feedback, or to the geometry of the Indian plate indentor, with the corner being thrust beneath the Asian plate resulting in buckling which accommodates shortening; both processes may be important. The northern third of the syntaxis corresponds to a steep domal ‘pop-up’ structure bounded by the India–Asia suture on three sides and a thrust zone to the south. Within the dome, Greater Himalaya rocks equilibrated at ~ 800 °C and 25–30 km depth during the Miocene, with these conditions potentially persisting into the latest Miocene and possibly the Pliocene, with modest decompression prior to ~ 4 Ma. This domal ‘pop-up’ corresponds to the area of youngest bedrock ages on a wide variety of thermochronometers and geochronometers. In this paper we review the extensive scientific literature that has focused on the eastern syntaxis and provide new chronological data on its bedrock and erosion products to constrain the age of inception of the very rapid uplift and erosion. We then discuss its cause, with the ultimate aim to reconstruct the exhumation history of the syntaxis and discuss the tectonic context for its genesis. We use zircon and rutile U–Pb, white mica Ar–Ar and zircon fission track dating methods to extract age data from bedrock, Brahmaputra modern sediments (including an extensive compilation of modern detrital chronometry from the eastern Himalaya) and Neogene palaeo-Brahmaputra deposits of the Surma Basin (Bangladesh). Numerical modelling of heat flow and erosion is also used to model the path of rocks from peak metamorphic conditions of ~ 800 °C to < 250 °C. Our new data include U–Pb bedrock rutile ages as young as 1.4 Ma from the Namche Barwa massif and 0.4 Ma from the river downstream of the syntaxis. Combined with existing data, our new data and heat flow modelling show that: i) the detrital age signature of the modern syntaxis is unique within the eastern Himalayan region; ii) the rocks within the domal pop-up were > 575 ± 75 °C only 1–2 Myr ago; iii) the Neogene Surma Basin does not record evidence of the rise and erosion of the domal pop-up until latest Pliocene–Pleistocene time; iv) Pleistocene exhumation of the north-easternmost part of the syntaxis took place at rates of at least 4 km/Myr, with bedrock erosion of 12–21 km during the last 3 Ma; v) the inception of rapid syntaxial exhumation may have started as early as 7 Ma or as late as 3 Ma; and vi) the Yarlung Tsangpo is antecedent and subsequently distorted by the developing antiform. Together our data and modelling demonstrate that the domal pop-up with its exceptional erosion and topographic relief is likely a Pleistocene feature that overprinted earlier structural and metamorphic events typical of Himalayan evolution.