Sediment Cladocera remains and geochemistry were analyzed at Lake Ledro, a small subalpine lake with a large catchment area located in northern Italy. The aim of the study was to investigate human, climate and hydrological impacts on the Cladocera community and on the geochemical components during the last few centuries. A sediment core was collected from the deepest point of Lake Ledro and radiometrically dated. Cladocera remains were analyzed to track the trophic lake evolution. The core bottom section revealed the dominance of Bosminidae in concomitance with nutrient pulses entering into the lake during major flood events. The abundance of species preferring cold water temperatures confirmed the deposition of this core section during the Little Ice Age. The flood event occurred in the first half of the 19th century produced a drastic increase in littoral species, due to the development of new habitats. The decrease in Cladocera densities during the following lake stage was followed by a rapid increase in planktonic species during the nutrient enrichment after the 1960s. Statistical analyses revealed a clear response of Cladocera community to climate variability during oligotrophic periods, while no relation to temperature changes was recorded during high nutrient levels. A preliminary study on Bosminidae and Daphnidae body size and appendages length was carried out to reconstruct major changes in the lake food web. Only Bosmina spp. revealed clear body size changes: minor shifts were recorded before the 1930s in relation to the low nutrient concentrations, while the major changes occurred during the 1980s were interpreted as related to the appearance of Cladocera invertebrate predators. Geochemical components were studied using X-ray fluorescence spectroscopy (XRF) analysis in order to recognize the impact of the large catchment area and from the lake-level regulations on the lake hydrology. Moreover the Si:Al ratios profile confirmed the increase in lake productivity after the 1960s. Although both Cladocera and geochemical analysis indicate major changes since the 1960s, they also revealed diverse responses to common external and local forcing, thus confirming the value of a multi-proxy approach for disentangling the lake responses to different environmental stressors. Moreover, it outlined the importance of larger catchment areas on small lakes as they are to a larger extent influenced by the modifications occurring in the drainage basin.