The Late Cenozoic tectonics in the Eastern Carpathians and the Pamir-Hindu Kush region are compared to ascertain structural position and origin of strong mantle earthquakes in the Vrancea and Hundu Kush megasources. Intensive Oligocene–Quaternary deformation took place in the Pamir-Hindu Kush region. Under compressive regime, large upper crust blocks were detached and displaced up to several hundred kilometers. Relics of the oceanic crust of the Precambrian, Hercynian Paleo-Tethys and Early Meso-Tethys were overthrusted by the upper crust blocks and subsided to the depth of 40–70 km, where they were metamorphosed into higher density metabasites of the granulite-eclogite type. In the Pliocene–Quaternary, the region was quickly elevated, mainly because of decrease of density of the upper mantle. As a result, the detached dense metabasite slab began to move down to the depths of 270–300 km. The same processes took place in the Vrancea area. The basic rocks of the Inner Carpathian zones were moved and underthrusted the Moesian Platform with simultaneous overthrusting by the Outer Carpathian zone. Under the load of the Outer zone nappes and the Focsani basin sediments, the basic rocks were metamorphosed into the dense metabasite slab. After decrease of the upper mantle density because of asthenospheric convection beneath the Carpathians, the slab began to move downwards. Destruction of the moving slabs produced the mantle earthquakes.