The Bohemian Massif in the Central European Variscides contains many crustal slices with (ultra-)high-pressure rocks related to continent-continent collision. After closure of pre-existing oceans during the Devonian, excess crustal thickness was maintained for about 50 Ma until at around 340 Ma large volumes of high-pressure rocks from the crustal root were exhumed within a few million years. We relate this event to delamination and complete detachment of the lithospheric mantle, causing a crustal-scale isostatic instability. In the Erzgebirge dome, a model region in the northern part of the massif, an array of interrelated PTtd-paths with “decompression/cooling” and “decompression/heating” trajectories in juxtaposed tectonometamorphic units has been established. Numerical 2D-experiments using a rheologically, thermally and dynamically consistent convection technique show three stages of the crustal evolution related to delamination and detachment of mantle lithosphere under the crustal root: (1) During delamination a rapid overthickening of the crust can occur with the crust penetrating down to >160 km depth. (2) After detachment extensional crustal thinning controlling exhumation occurs with escape of rocks from the crustal root towards the margins of the orogen through tectonically weak zones. Horizontal displacement exceeds vertical by a factor of ∼3. (3) Forced circulation in the weak zones follows and upward flow of lower crustal rocks is compensated by subduction of upper crustal rocks in the footwall of these zones. One-dimensional modelling was used in order to further understand basic processes and to simulate the rock record in detail. According to 2D and 1D modelling, strongly decelerating exhumation rates with decreasing overburden and a late increase in the geothermal gradient due to upward heat transfer are necessary corollaries of this scenario, in keeping with observations from the Erzgebirge dome. Exhumation PT-paths do not conform to one single uniform exhumation trajectory; rather, assemblages of interrelated PTtd-paths are characteristic.