The Cape Fear Slide is one of the largest (>25 000 km³) submarine slope failure complexes on the US Atlantic margin. Here we use a combination of new high-resolution multichannel seismic data (MCS) from the National Science Foundation Geodynamic Processes at Rifting and Subducting Margins (NSF GeoPRISMS) Community Seismic Experiment and legacy industry MCS to derive detailed stratigraphy of this slide and constrain the conditions that lead to slope instability. Limited outer-shelf and upper-slope accommodation space during the Neogene, combined with lowstand fluvial inputs and northwards Gulf Stream sediment transport, appears to have contributed to thick Miocene and Pliocene deposits that onlapped the lower slope. This resulted in burial of an upper-slope bypass zone developed from earlier erosional truncation of Paleogene strata. These deposits created a broad ramp that allowed accumulation of thick Quaternary strata across a low-gradient (<3.5°) upper slope. Upslope of one of the larger headwalls, undulating Quaternary strata appear to downlap onto a buried failure plane. Many of the nested headwalls of the upper-slope portion of slide complex are underlain by deformed strata, which may be the result of fluid migration associated with localized subsidence from salt migration. These new data and observations suggest that antecedent margin physiography, sediment loading and substrate fluid flow were key factors in preconditioning the Cape Fear slope for failure.