The Taihu Lake ecosystem has been subjected to numerous anthropogenic stressors during the past decades, leading to substantial changes in nutrient dynamics and habitat quality. For instance, the northwestern lake bays receive large amounts of nutrient-rich wastewater and have frequently experienced algal blooms, while the eastern lake region is still dominated by submersed macrophytes. Such changes in environmental characteristics can greatly impact benthic macroinvertebrate communities. We used a 15-year monitoring data series collected by the Taihu Laboratory for Lake Ecosystem Research to examine the spatial and temporal variations of the benthic invertebrate fauna and evaluate its status and trends. We found that three major communities could be distinguished based on taxonomic group composition and abundance, and these corresponded well with three lake habitat types: algal-dominated, macrophyte-dominated, and open-lake zone. An analysis of temporal trends showed major changes in the macroinvertebrates during the study period, largely driven by a lake-wide and significant decline in the abundance of pollution-tolerant taxa. The spatial and temporal variations of macroinvertebrate communities were mainly explained by nutrients (e.g., total nitrogen and ammonium concentrations) and habitat factors (e.g., sediment substrates and macrophyte biomass) as indicated by Random Forests regression, but the major drivers of macroinvertebrate density differed among the three lake zones at the temporal scale. Moreover, our findings suggest that benthic invertebrates were more sensitive to the improvement of the lake's environmental conditions than the pelagic community was. This study provides insights into the responses of macroinvertebrates to ecological dynamics in lakes and highlights the importance of continued monitoring for tracking long-term changes.