Invasion of Mysis diluviana from upstream stockings drastically altered the food web of 480 km 2 Flathead Lake, Montana (USA). Mysis increased exponentially after establishment in 1982, preying upon large zooplankters, thereby substantially altering zooplankton community composition, favoring small-sized species. In consequence, primary production increased by 21% owing to changes in zooplankton feeding efficiency. Moreover, the abundant Mysis provided forage for the nonnative lake trout that also rapidly expanded, causing concomitant extirpation of kokanee salmon and near loss of native fishes. This has become a case history of how introduced species can mediate trophic cascades. Here we examine the long-term (1982-2014) dynamics of Mysis in Flathead Lake and how distribution and abundance of this invasive species is related to chemical, physical, and biological factors. We show that Mysis is a strong interactor, regulating zooplankton and phytoplankton biomass interactively with nutrient (N and P) dynamics. Moreover, changes in life history and changing spatial dynamics are strengthening the regulatory role of the Mysis, despite seemingly strong top-down pressure via predation of the Mysis by lake trout. The Mysis are structuring nearly all interactions within and between the biota of Flathead Lake.