Deterioration of aquatic ecosystems, as a consequence of human-induced disturbances, is a critical global concern. To fully understand the responses of aquatic systems to anthropogenic impacts, it is crucial to assess long-term changes in lakes. The water quality of Jili Lake, a large water body in northwest China, has deteriorated recently, owing to the growing impacts of regional warming and human activities. Thus, Jili Lake was a prime candidate for evaluation of historical multi-stressor impacts. Meteorological data, historical documents, and assemblages of cladoceran microfossils in the sediments of Jili Lake were employed to investigate changes in the cladoceran community over the past century, and to evaluate the response of that aquatic community to human activities. From the 1920s to the 1950s, species richness of the cladoceran community was high, which reflected conditions of relatively low human impact. From the 1960s to 1970s, a sharp decrease in Bosmina longirostris, a planktonic cladoceran species, suggested a decrease in water level as a result of dam construction and intensified water exploitation. Since the 1980s, the water level in the lake has been restored, but increased fish farming and construction of a water storage facility caused salinisation and eutrophication of Jili Lake. Accordingly, the cladoceran community displayed distinct signs of a regime shift, with a gradual transition to dominance of B. longirostris and a sharp decrease in littoral species (e.g. Leydigia leydigi, L. acanthocercoides, Alona quadrangularis, Alona affinis). Our results suggest that human-induced disturbances were the main factor that drove changes in the cladoceran community since about the mid-20th century.