Two invasive mussels (zebra mussel, Dreissena polymorpha and quagga mussel D. rostriformis bugensis) have restructured the benthic habitat of many water bodies in both Europe and North America. Quagga mussels dominate in most lakes where they co-occur even though zebra mussels typically invade lakes first. A reversal to zebra mussel over time has rarely been observed. Laboratory experiments have shown that quagga mussels grow faster than zebra mussels when predator kairomones are present and this faster growth is associated with lower investment in anti-predator response in quagga mussels than zebra mussels. This led to the hypothesis that the dominance of quagga mussels is due to faster growth that is not offset by higher vulnerability to predators when predation rates are low, as may be expected in newly colonized lakes. It follows that in lakes with high predation pressure, the anti-predatory investments of zebra mussels should be more advantageous and zebra mussels should be the more abundant of the two species. In Onondaga Lake, NY, a meso-eutrophic lake with annual mussel surveys from 2005 to 2018, quagga mussels increased from less than 6% of the combined mussel biomass in 2007 to 82% in 2009 (from 3 to 69% by number), rates typical of this displacement process elsewhere, but then declined again to 11–20% of the mussel biomass in 2016–2018. Average total mussel biomass also declined from 344–524 g shell-on dry weight (SODW)/m² in 2009–2011 to 34–73 g SODW/m² in 2016–2018, mainly due to fewer quagga mussels. This decline in total mussel biomass and a return to zebra mussel as the most abundant species occurred as the round goby (Neogobius melanostomus) increased in abundance. Both the increase to dominance of quagga mussels and the subsequent decline following the increase in this molluscivorous fish are consistent with the differences in the trade-off between investment in growth and investment in defenses of the two species. We predict that similar changes in dreissenid mussel populations will occur in other lakes following round goby invasions, at least on the habitats colonized by both species.