Herein, we document changes in the Lake Michigan food web between 1970 and 2000 and identify the factors responsible for these changes. Control of sea lamprey (Petromyzon marinus) and alewife (Alosa pseudoharengus) populations in Lake Michigan, beginning in the 1950s and 1960s, had profound effects on the food web. Recoveries of lake whitefish (Coregonus clupeaformis) and burbot (Lota lota) populations, as well as the buildup of salmonine populations, were attributable, at least in part, to sea lamprey control. Based on our analyses, predation by salmonines was primarily responsible for the reduction in alewife abundance during the 1970s and early 1980s. In turn, the decrease in alewife abundance likely contributed to recoveries of deepwater sculpin (Myoxocephalus thompsoni), yellow perch (Perca flavescens), and burbot populations during the 1970s and 1980s. Decrease in the abundance of all three dominant benthic macroinvertebrate groups, including Diporeia, oligochaetes, and sphaeriids, during the 1980s in nearshore waters ([Formula: see text]50 m deep) of Lake Michigan, was attributable to a decrease in primary production linked to a decline in phosphorus loadings. Continued decrease in Diporeia abundance during the 1990s was associated with the zebra mussel (Dreissena polymorpha) invasion, but specific mechanisms for zebra mussels affecting Diporeia abundance remain unidentified.