To better understand the feeding ecology of two important Laurentian Great Lakes prey species, rainbow smelt Osmerus mordax and emerald shiners Notropis atherinoides, we quantified the diet composition, selectivity, daily ration, and diet overlap of both species in offshore central Lake Erie during May through October 2005, which spanned a period of severe hypolimnetic hypoxia (<2 mg O₂/L). Rainbow smelt fed upon a variety of prey taxa, including zooplankton, chironomid pupae and larvae, and fish, whereas emerald shiners primarily consumed cladocerans, if available. In turn, diet overlap between rainbow smelt and emerald shiners was low except during September when hypolimnetic hypoxia reduced rainbow smelt access to benthic prey. Rainbow smelt most frequently selected chironomid pupae, while emerald shiners generally selected pupae or large predatory cladocerans (Leptodora or Bythotrephes). Daily ration and individual consumption by rainbow smelt were 54–68% less during hypoxia than at the same site during stratified pre-hypoxic or mixed post-hypoxic conditions. Although emerald shiner daily ration and individual consumption decreased between pre-hypoxic and hypoxic periods, it continued to decrease during the post-hypoxic period, suggesting that reduced consumption may not have been linked to hypoxic conditions. Ultimately, our findings suggest that emerald shiners are as important regulator of zooplankton abundance in the Great Lakes as rainbow smelt, given their potentially high mass-specific consumption rates, selectivity and diet patterns, and current high abundance.