Southern Lake Michigan has changed in response to alterations in nutrients and invasive species. NOAA and EPA monitoring results are used to examine those changes. NOAA provides detailed seasonal resolution, but limited spatial coverage, whereas the EPA provides more spatial coverage, but limited seasonal resolution. We compare changes in total phosphorus (TP), silica, nitrate plus nitrite, and chlorophyll concentrations from before and after the invasion by the quagga mussel (Dreissena rostriformis bugensis). Although TP at NOAA stations was consistently higher than at EPA stations, both confirm declines in spring and summer surface mixed layer (SML) conditions. Chlorophyll differed at EPA and NOAA stations before quagga mussel invasion, but not after the invasion. Spring chlorophyll decreased at NOAA stations after the invasion, but summer conditions did not change at either set of stations. Pre-invasion silica at NOAA stations was slightly higher than at EPA stations, and the lake's Si reservoir increased over the study period. Basin-scale spring Si increased gradually, whereas summer SML Si increased dramatically after 2003, likely reflecting reduced diatom production. Basin-scale nitrate increased significantly from pre- to post-invasion in both spring and summer. Summer nitrate utilization declined drastically in recent years, likely reflecting reduced phytoplankton production. TP loads decreased; however, the timing of changes in chlorophyll and Si and nitrate utilization suggest the recent increase in dreissenid filtering dramatically reduced spring phytoplankton abundance and production across the entire southern basin. The offshore pelagic zone of the historically mesotrophic southern Lake Michigan is now similar to oligotrophic Lake Superior.