Although the effects of interactions between turbidity currents and the seabed have been widely studied, the roles of substrate and bathymetry on the emplacement of mass-transport complexes (MTCs) remain poorly constrained. This study investigates the effect of bathymetric variability and substrate heterogeneity on the distribution, morphology, and internal characteristics of nine MTCs imaged within a 3D seismic volume in the southern Magdalena Fan, offshore Colombia. The MTCs overlie substrate units composed mainly of channel–levee-complex sets, with subsidiary deposits of MTCs. MTC dispersal was influenced by tectonic relief, associated with a thin-skinned, deep-water fold-and-thrust belt, and by depositional relief, associated with the underlying channel–levee-complex sets; it was the former that exerted the first-order control on the location of mass-transport pathways. Channel–levee-complex sets channelized, diverted, or blocked mass flows, with the style of response largely controlled by their orientation with respect to the direction of the incoming flow and by the height of the levees with respect to flow thickness. MTC erosion can be relatively deep above channel-fill deposits, whereas more subtle erosional morphologies are observed above adjacent levee units. In the largest MTC, the distribution of the seismic facies is well imaged, being influenced by the underlying bathymetry, with internal horizontal contraction occurring updip of bathymetric highs, erosion and bypass predominating above higher gradient slopes, and increased disaggregation characterizing the margins. Hence, bathymetric irregularities and substrate heterogeneity together influence the pathways, geometries, and internal characteristics of MTCs, which could in turn influence flow rheology, runout distances, the presence and continuity of underlying reservoirs, and the capacity of MTCs to act as either hydrocarbon seals or reservoirs.