Large lakes, such as Lake Simcoe, Ontario, Canada, are undergoing significant change due to local and global stressors. Uni- and multivariate analyses of Lake Simcoe's zooplankton community from 1986 to 2012 indicated multiple events of ecosystem change that were synchronous across three lake stations . In the mid-1990s, shifts in zooplankton species abundance and richness, and total cladoceran body size were strongly correlated with the invasion of the zooplanktivore, Bythotrephes cederstroemii. In the early 2000s, additional shifts in zooplankton abundance, as well as copepod body size, coincided with increased water clarity (linked to filter feeding by the invader Dreissena polymorpha) and hypolimnetic water temperature. Further community changes occurred in the 2000s when Bythotrephes declined and many vulnerable cladoceran species recovered. However, the Lake Simcoe community did not fully return to its pre-invasion state as the cold-water herbivores, Daphnia longiremis and Daphnia pulicaria, remained absent. The Lake Simcoe zooplankton community illustrates ongoing ecosystem change that propagated throughout the lake food web and may be reflected in other lakes experiencing global stressors of climate change and species invasions.