Where a stream enters a large lake, the mouth represents a transitional environment that is neither truly lotic nor lentic in nature and therefore is likely to affect the fauna present. Theory on habitat area and stream size predicts that species richness will increase farther downstream as watershed size increases, but as stream gradient and thus flow rate declines, stream mouths present a different and understudied habitat. Freshwater mussels in the family Unionidae are in decline, and therefore understanding how they respond across diverse habitats is also critical. We sampled mussel assemblages from 2010 to 2012 in the lower reaches of twelve small tributaries and two large embayments of the western and central basins of Lake Erie, where watershed size ranged from 10 to 4000 km². These watersheds were assessed for land use by remote sensing and for basic water chemistry and the composition of their benthos by standard protocols. Evidence of native unionid mussels occurred in all watersheds, with 14 species found alive, which make up 75% of mussel species still present throughout Lake Erie. A species-area relationship occurred, although the effect was weaker than that present for flowing streams in the region. Additionally, the habitat and corresponding assemblages were characterized as depositional in nature, which logically follow high agricultural land use and corresponding high levels of turbidity and the proportion of silt and clay. Therefore, the lake environment influenced mussel assemblages, yet these conditions appear to limit dreissenid mussels in river mouths.