Waves and currents create bottom shear stress, a force at the seabed that influences sediment texture distribution, micro-topography, habitat, and anthropogenic use. This paper presents a methodology for assessing the magnitude, variability, and driving mechanisms of bottom stress and resultant sediment mobility on regional scales using numerical model output. The analysis was applied to the Middle Atlantic Bight (MAB), off the U.S. East Coast, and identified a tidally-dominated shallow region with relatively high stress southeast of Massachusetts over Nantucket Shoals, where sediment mobility thresholds are exceeded over 50% of the time; a coastal band extending offshore to about 30 m water depth dominated by waves, where mobility occurs more than 20% of the time; and a quiescent low stress region southeast of Long Island, approximately coincident with an area of fine-grained sediments called the “Mud Patch”. The regional high in stress and mobility over Nantucket Shoals supports the hypothesis that fine grain sediment winnowed away in this region maintains the Mud Patch to the southwest. The analysis identified waves as the driving mechanism for stress throughout most of the MAB, excluding Nantucket Shoals and sheltered coastal bays where tides dominate; however, the relative dominance of low-frequency events varied regionally, and increased southward toward Cape Hatteras. The correlation between wave stress and local wind stress was lowest in the central MAB, indicating a relatively high contribution of swell to bottom stress in this area, rather than locally generated waves. Accurate prediction of the wave energy spectrum was critical to produce good estimates of bottom shear stress, which was sensitive to energy in the long period waves.