This paper examines the relationship between seismogenic thickness, lithosphere structure and rheology in central and northeastern Asia. We accurately determine earthquake depth distributions which reveal important rheological variations in the lower crust. These variations exert a fundamental control on the active tectonics and the morphological evolution of the continents. We consider 323 earthquakes across the Tibetan Plateau, the Tien Shan and their forelands as well as the Baikal Rift, NE Siberia and the Laptev Sea and present the source parameters of 94 of these here for the first time. These parameters have been determined through body wave inversion, the identification of depth phases or the modelling of regional waveforms. Lower crustal earthquakes are found to be restricted to the forelands in areas undergoing shortening, and to locations where rifting coincides with abrupt changes in lithosphere thickness, such as the NE Baikal Rift and W Laptev Sea. The lower crust in these areas is seismogenic at temperatures that may be as high as 600°C, suggesting that it is anhydrous, and is likely to have great long-term strength. Lower crustal earthquakes are therefore a useful proxy indicating strong lithosphere in places that are too small in areal extent for this to be confirmed independently by estimating effective elastic thickness from gravity–topography relations. The variation in crustal rheology indicated by the distribution of lower-crustal earthquakes has many implications ranging from the support of mountain belts and the formation of steep mountain fronts, to the localization and orientation of rifting. In combination, these processes can also be responsible for the separation of the front of the thin-skinned mountain belts from their hinterlands when continents separate.