Tai Lake (Chinese: Taihu), the third-largest freshwater lake in China, suffers from harmful cyanobacteria blooms that are caused by economic development and population growth near the lake. Several studies have focused on phytoplankton in Tai Lake after a drinking water crisis in 2007; however, these studies primarily focused on microcystin bioaccumulation and toxicity to individual species without examining the effects of microcystin on macrobenthic community diversity. In this study, we conducted a survey of the lake to examine the effects of microcystine and other pollutants on marcobenthic community diversity. A totally of forty-nine species of macroinvertebrates were found in Tai Lake. Limnodrilus hoffmeisteri and Corbicula fluminea were the most abundant species. Cluster-analysis and one-way analysis of similarity (ANOSIM) identified three significantly different macrobenthic communities among the sample sites. More specifically, sites in the eastern bays, where aquatic macrophytes were abundant, had the highest diversity of macrobenthic communities, which were dominated by Bellamya aeruginosa, Bellamya purificata, L. hoffmeisteri, and Alocinma longicornis. Sites in Zhushan Bay contained relatively diverse communities, mainly composed of L. hoffmeisteri, C. fluminea, L. claparederanus, R. sinicus, and Cythura sp. Sites in the western region, Meiliang Bay and Wuli Bay had the lowest diversity, mainly composed ofL. hoffmeisteri, C. fluminea, Branchiura sowerbyi, and Rhyacodrilus sinicus. In addition, the relationships between macrobenthic metrics (Shannon–Wiener, Margalef, and Pielou) and environmental variables showed that community structure and spatial patterns of macrobenthos in Tai Lake were significantly influenced by chemical oxygen demand (COD_Cr), biochemical oxygen demand (BOD₅), lead (Pb), and microcystin-LR (L for leucine and R for arginine). Our findings provide critical information that could help managers and policymakers assess and modify ecological restoration practices.