Ecological stability in the Laurentian Great Lakes has been altered by nonindigenous species, such as the Round Goby Neogobius melanostomus and dreissenid mussels, and by declines in native amphipods Diporeia spp. We evaluated whether these changes could influence diet overlap between three benthivorous fishes (Slimy Sculpin Cottus cognatus, Deepwater Sculpin Myoxocephalus thompsonii, and Round Goby) and whether predation on eggs of native species was occurring. We examined diets of fish collected at depths of 69–128 m in Lake Michigan offshore of Frankfort and Muskegon, Michigan, and Two Rivers and Sturgeon Bay, Wisconsin, during January–May 2009 and 2010. Important prey (by dry weight proportion and by percent frequency of occurrence) for Slimy Sculpin were Mysis (0.34; 45%), Diporeia (0.16; 34%), and Limnocalanus macrurus (0.22; 68%); important prey for Deepwater Sculpin were Mysis (0.74; 92%) and Diporeia (0.16; 54%). Round Goby consumed mainly bivalves (i.e., dreissenids: 0.68; 95%) and Mysis (0.15; 37%). The two sculpin species consumed the eggs of Bloaters Coregonus hoyi (Slimy Sculpin: 0.04, 11%; Deepwater Sculpin: 0.02, 7%) and the eggs of Deepwater Sculpin (Slimy Sculpin: 0.03, 13%; Deepwater Sculpin: 0.05, 16%) during February–May at all sites. Round Goby also consumed eggs of these species but at lower levels (≤0.01; <1%). Diet overlap was identified between sculpin species at Frankfort and Sturgeon Bay, suggesting possible interspecific competition, but their diets did not overlap at Two Rivers; diet overlap was never observed between Round Goby and either sculpin species. Given that (1) diet overlap varied by site and (2) diet proportions varied spatially more than temporally, benthivores appear to be exhibiting localized responses to recent ecological changes. Overall, these results reveal that egg predation and interspecific competition could be important interactions to consider in future examinations of the population dynamics of these species or in ecosystem models that forecast how fisheries will respond to possible perturbations or management scenarios.