Understanding specific pathways for sand transport in the lower reaches of large rivers, including the Mississippi, is a key for addressing multiple significant geologic problems, such as delta building and discharge to the oceans, and for environmental restoration efforts in deltaic environments threatened by rising sea levels. Field studies were performed in the Mississippi River 75–100 km upstream of the Gulf of Mexico outlet in 2010–2011 to examine sand transport phenomena in the tidally affected river channel over a range of discharges. Methods included mapping bottom morphology (multibeam sonar), cross-sectional and longitudinal measurements of water column velocity and acoustic backscatter, suspended sediment sampling, and channel-bed sampling. Substantial interaction was observed between the flow conditions in the river (boundary shear stress), channel-bed morphology (size and extent of sandy bedforms), and bed material sand transport (quantity, transport mode, and spatial distribution). A lateral shift was observed in the region of maximum bed material transport from deep to shallow areas of subaqueous sand bars with increasing water discharge. Bed material was transported both in traction and in suspension at these water discharges, and we posit that the downriver flux of sand grains is composed of both locally- and drainage basin-sourced material, with distinct transport pathways and relations to flow conditions. We provide suggestions for the optimal design and operation of planned river diversion projects.