The distribution of earthquakes in stable intracontinental tectonic settings is typically far more diffuse than along plate boundaries and the causative mechanisms underlying some recognizable clustering are not understood. Here we show that seismicity in intraplate western and central Europe is largely limited to regions that exhibit a low-density layer in the uppermost lithospheric mantle and preferentially clustered above lateral gradients in upper mantle effective viscosity. The basis for these new insights into the thermal and density configuration of the upper mantle is provided by a shear-wave tomographic model. We propose that the spatial correlations between mantle low-density bodies and crustal seismicity reflect the importance of buoyancy forces within the mantle lithosphere. In addition, under the interaction of forces due to mantle gravitational instabilities, plate tectonics and postglacial rebound, the variably hot and strong mantle lithosphere responds by localized deformation which imposes differential loading on the overlying crust.