A joint analysis of global seismicity and seismic tomography indicates that the seismic potential of continental intraplate regions is correlated with the seismic properties of the lithosphere. Archean and Early Proterozoic cratons with cold, stable continental lithospheric roots have fewer crustal earthquakes and a lower maximum earthquake catalog moment magnitude (Mcmax). The geographic distribution of thick lithospheric roots is inferred from the global seismic model S40RTS that displays shear-velocity perturbations (δVS) relative to the Preliminary Reference Earth Model (PREM). We compare δVS at a depth of 175 km with the locations and moment magnitudes (Mw) of intraplate earthquakes in the crust (Schulte and Mooney, 2005). Many intraplate earthquakes concentrate around the pronounced lateral gradients in lithospheric thickness that surround the cratons and few earthquakes occur within cratonic interiors. Globally, 27% of stable continental lithosphere is underlain by δVS≥3.0%, yet only 6.5% of crustal earthquakes with Mw>4.5 occur above these regions with thick lithosphere. No earthquakes in our catalog with Mw>6 have occurred above mantle lithosphere with δVS>3.5%, although such lithosphere comprises 19% of stable continental regions. Thus, for cratonic interiors with seismically determined thick lithosphere (1) there is a significant decrease in the number of crustal earthquakes, and (2) the maximum moment magnitude found in the earthquake catalog is Mcmax=6.0. We attribute these observations to higher lithospheric strength beneath cratonic interiors due to lower temperatures and dehydration in both the lower crust and the highly depleted lithospheric root.