In this study, for the first time, using similar methods, we compared the population density and distribution across different substrate types of Limnoperna fortunei and Dreissena polymorpha, as well as their impacts on the composition of benthic communities. Data on L. fortunei were obtained in Rio Tercero Reservoir, Argentina, whereas studies on D. polymorpha were conducted in North America and Europe. We found that, similar to the zebra mussel, L. fortunei creates high densities on hard substrates in the littoral zone, and avoids soft substrates in the profundal zone; however, the overall population density of L. fortunei in a water body seems to be higher than that of zebra mussels. Additional studies on Limnoperna are needed to confirm this hypothesis. The effect of L. fortunei on macrobenthos is very similar to the effect of D. polymorpha and is associated with an increase in the overall diversity, density, and biomass of native macroinvertebrates in druses compared with bare sediments. The presence of L. fortunei druses in the littoral zones of Río Tercero has increased the average species richness of native benthic invertebrates per sample by almost 70% and their density and biomass by threefold, positively affecting epifaunal organisms and negatively burrowing invertebrates and unionids. In the near future, the freshwaters of North America may be colonized by L. fortunei, resulting in strong impacts on entire invaded ecosystems and devastating impacts on native unionids, especially in the southern regions of the United States, which are not colonized with dreissenids.