The pollution of water bodies has deteriorated the quality of freshwater and the health of the natural ecosystem. In the present study, the water quality index (WQI) was used to evaluate the spatial and temporal contamination levels in Lake Yuriria, Guanajuato, Mexico. Water quality was monitored at 27 different locations (monitoring points) in the dry season (April) and after the rainy season (November), measuring 21 physicochemical water parameters, 2 biological parameters, and 19 metal concentrations. The data analysis revealed that Yuriria Lake is a eutrophic water body. Six monitoring points exhibited a poor WQI (25–50) in April, and seven monitoring sites were classified as having poor water quality in November. The remaining monitoring points showed a WQI categorized as fair (51–70) in both periods. The present study analyzes an extensive distribution of monitoring points over the lake’s surface in two periods, showing a significant spatial and temporal representation of water quality. In addition, the major pollution sources identified include agricultural runoff and effluents from a nearby waterway and freshwater river. Finally, the key physicochemical parameters that determined the water quality were identified. BOD₅, NH₄⁺, P, orthophosphates, DO, conductivity, TSS, and color were linked to anthropogenic pollution sources, and Li, Ni, Zn, Cd, Ba, and Pb concentrations were linked to natural contamination sources. This study demonstrates the utility and versatility of these methodologies in water quality research, and it is the first spatial and temporal WQI analysis of Yuriria Lake.