River plumes discharging into continental shelf waters have the potential to influence patchiness of larval fishes, prey, and gelatinous predators. Using a high-resolution plankton imaging system, we sampled larval fishes, copepods, and planktonic predators (ctenophores, hydromedusae, and siphonophores) across multiple freshwater pulses exiting the mouth of Mobile Bay (Alabama, USA) into the northern Gulf of Mexico in April before, during, and immediately after the largest flood event of 2016. Water column profiles were used to quantify changes in the vertical and horizontal structure of planktonic distributions, enabling a fine-scale examination of the predator and prey fields across distinct plume regimes. Before the peak flood event, the water column was highly stratified and high-density concentrations of fish larvae and zooplankton were observed in nearby regions of hydrodynamic convergence. This situation potentially provided a rich feeding environment for larvae but also subjected them to increased predation pressure. As the plume flow strengthened and the water column became more turbulent, fish larvae were advected offshore by strong currents and subjected to highly turbulent conditions of wind-forcing and mixing processes of the plume. The plume outflow was sampled with a multinet system to measure the effects of entrainment within a plume at the scale of an individual fish larva. Each net tow was classified as having sampled one of two distinct water masses based on known salinity values: either plume (salinity <25) or shelf (salinity >32). Size frequency distributions of larval striped anchovy (Anchoa hepsetus) and sand seatrout (Cynoscion arenarius) indicated that larger individuals were present in shelf waters but absent from plumes. Sagittal otolith microstructure analysis revealed that recent growth of both focal species was significantly lower for plume-residents during the last few days prior to capture. Furthermore, plume-residents were in poorer morphometric condition (e.g., skinnier at length) than their shelf counterparts. Additionally, diet analyses suggested that plume-residents may have been feeding on a poorer quality diet (comprised substantially of small phytoplankton as opposed to more nutritious copepods) than those captured from shelf waters. Taken together, these results suggest that larval survival is negatively affected by river plume physical processes and that there are biological consequences for marine fish larvae that encounter high-magnitude plume regimes.