Rapid degradation of freshwater ecosystems threatens water supply for human populations and natural landscapes. At diverse time scales, this process has been clearly associated with climatic and anthropogenic forcings. The question remains, however, how tropical lakes have responded to these two sources of variability. We present a multiproxy record from Lake San Lorenzo, Lagunas de Montebello National Park, tropical Mexico, spanning the last ~3400 years. We used multi‐elemental concentrations, and Cladocera and pollen assemblages along the record to reconstruct regional and local environmental variability, aiming to infer the factors and processes involved in the evolution of the lacustrine system. A principal component analysis on the pooled biological and geochemical evidence allowed the inference of the main changes in lake level and productivity. At millennial scales, the development of the lake system has been closely associated with regional moisture availability, with wetter (drier) time intervals associated with high (low) lake stands. According to Ti concentrations, from ~3400 to 1000 cal. a BP, regional conditions followed a trend towards drier conditions, with littoral cladoceran assemblages suggesting high lake productivity. The extreme regional droughts reportedly associated with the cultural collapse of the Maya civilization manifested in our study area through both high lake productivity and the lowest lake levels of the record. Through the last ~800 years, the regional moisture availability has increased, with the water body becoming deeper and larger. Overall, our record offers evidence of a highly variable system strongly coupled with regional climates, but also very sensitive to local disturbances associated with human occupation. Lake San Lorenzo has been highly resilient to external pressures and has previously recovered from conditions probably alike those associated with the ongoing modern deterioration process. Nevertheless, such recovery involves a complex network of interactions amongst natural and human factors.