Abstract We present results from thermo‐mechanical numerical modeling of interactions between thermal, thermo‐compositional, and purely compositional (hydrous) mantle plumes, and a rheologically layered lithosphere containing a mid‐lithospheric discontinuity (MLD). Our simulations show that mantle plume impact can effectively destabilize and delaminate cold, mature continental lithosphere. However, for the plume head to penetrate the lithosphere and initiate removal of the lower lithospheric mantle, a deep‐seated zone of weakness beneath the MLD is required. This vertically oriented zone could be an inherited tectonic suture and/or a domain of pervasive percolation of plume‐derived melts and/or fluids. In the context explored here, where a long‐lived plume is continuously fed from below, the conditions for plume‐induced craton destabilization appear to be less stringent than earlier assumed, as it can occur even with a thin MLD (≤10 km) and a purely hydrous plume lacking an initial thermal component.