Rivers are considered to be the primary means driving hydrological and geochemical fluxes between the continents and the ocean. However, it is unclear how well surface water fluxes represent total fluxes, or whether more diffuse subterranean fluxes of river water to the coastal ocean occur. This question is important in light of research demonstrating that submarine groundwater discharge (SGD) is important for geochemical and hydrological fluxes. Here, we examine the pathways and potential magnitude of the role that SGD plays in the Mississippi River Delta (MRD), the largest delta in North America. We present multiple independent lines of evidence demonstrating a hydrological connection between the Mississippi River (MR) and the MRD. Evidence includes hydrological budgets demonstrating downstream water losses from the MR, which are unexplained and are of the same magnitude as water sources to adjacent coastal bays of the MRD; well data indicating a correlation between groundwater height and the stage of the MR; and excess 222Rn inventories exceeding that expected from in situ production, implying an advective, i.e., groundwater source, to coastal bays. SGD likely flows from the MR to its delta via paleo- channels and other buried sand bodies. Seismic data indicates that such features are common, whereas resistivity data suggest the intrusion of low salinity water to coastal bays adjacent to the river. These results may be applicable to other deltas worldwide, as many of the world largest rivers have deltas with numerous abandoned distributaries that could act as conduits for groundwater.