Assessment of the mechanisms responsible for intraplate deformation and seismicity and the hazard intraplate earthquakes pose requires detailed knowledge of the rheology and crustal structure of plate interiors. To characterize the crustal structure of the Mid‐Atlantic United States, we generate receiver functions for 121 USArray, Pennsylvania State Seismic Network temporary deployment and permanent stations. We image a steep gradient in crustal thickness, in the transition from the Coastal Plain–Piedmont into the Valley and Ridge, which follows the orientation of the Appalachian orogen and a gradient in the gravity field. Cluster analysis of a uniform declustered seismicity catalog indicates that lateral variations in crustal thickness coincide with the spatial distribution of statistically significant persistent clusters of seismicity in the Mid‐Atlantic United States. This suggests that lateral variations in crustal structure, inherited from past orogenic and rifting processes, play a role in the concentration of stress and the spatial distribution of seismicity. The thicker continental crust appears to act as a buttress focusing stress and leading to a concentration of seismicity in the region of transition from thicker to thinner crust. In this scenario, strain would be expected to be uniformly distributed and earthquakes could have the potential to occur anywhere along the continuous region of lateral variations in crustal thickness in the Mid‐Atlantic United States.