Multiple styles of failure, ranging from densely spaced, mass transport driven canyons to the large, slab-type slope failure of the Currituck Slide, characterize adjacent sections of the central U.S. Atlantic margin that appear to be defined by variations in geologic framework. Here we use regionally extensive, deep penetration multichannel seismic (MCS) profiles to reconstruct the influence of the antecedent margin physiography on sediment accumulation along the central U.S. Atlantic continental shelf-edge, slope, and uppermost rise from the Miocene to Present. These data are combined with high-resolution sparker MCS reflection profiles and multibeam bathymetry data across the Currituck Slide Complex. Pre-Neogene allostratigraphic horizons beneath the slope are generally characterized by low gradients and convex downslope profiles. This is followed by the development of thick, prograded deltaic clinoforms during the middle Miocene. Along-strike variations in morphology of a regional unconformity at the top of this middle Miocene unit appear to have set the stage for differing styles of mass transport along the margin. Areas north and south of the Currituck Slide are characterized by oblique margin morphology, defined by an angular shelf-edge and a relatively steep (> 8°), concave slope profile. Upper slope sediment bypass, closely spaced submarine canyons, and small, localized landslides confined to canyon heads and sidewalls characterize these sectors of the margin. In contrast, the Currituck region is defined by a sigmoidal geometry, with a rounded shelf-edge rollover and gentler slope gradient (< 6°). Thick (> 800 m), regionally continuous stratified slope deposits suggest the low gradient Currituck region was a primary depocenter for fluvial inputs during multiple sea level lowstands. These results imply that the rounded, gentle slope physiography developed during the middle Miocene allowed for a relatively high rate of subsequent sediment accumulation, thus providing a mechanism for compaction–induced overpressure that preconditioned the Currituck region for failure. Detailed examination of the regional geological framework illustrates the importance of both sediment supply and antecedent slope physiography in the development of large, potentially unstable depocenters along passive margins.