In the Yucatán Peninsula, anthropogenic activities such as urbanization and the final disposal of solids and wastewater critically impact aquatic systems. Here, we evaluated the anthropogenic-related environmental alteration of Lake La Sabana, located in the northern limits of one of the main cities of the Mexican Caribbean. We evaluated lake water quality, using physical, chemical, and microbiological indicators, and heavy metals in surficial sediment and fish tissue to evaluate the potential environmental risk. Multivariate analyses revealed that environmental conditions in La Sabana are spatially and temporally heterogeneous. Medium to bad water quality was determined within different basins by the National Sanitation Foundation water quality index, related to the degree of anthropogenic influence at each zone. The central-south zones displayed critical microbiological values largely exceeding national standards. Heavy metals in sediment and fish tissue such as Zn and Hg were relatively low, but Hg concentrations threaten the ecological environment. Incipient wastewater treatment and its final disposal in La Sabana are mainly responsible for the changes in the trophic status and availability of nutrients, which in turn may have promoted changes in the biological structure and aquatic plant invasions. Lake La Sabana can be considered a model of the potential and sequential effects of anthropogenic alterations in the oligotrophic karst tropical aquatic systems in the Yucatan Peninsula.