Population growth, poorly planned industrial development and uncontrolled production processes have left a significant footprint of environmental deterioration in the Alto Atoyac watershed. In this study, we propose using the integrated pollution index (PI) to characterize the temporary variations in surface water quality during the rapid urbanization process in the municipalities of San Martín Texmelucán (SMT) and Tepetitla de Lardizabal (TL), in the states of Puebla and Tlaxcala, between 1985 and 2020. We assessed the correlation between the population growth rate and the water quality parameters according to the Water Quality Index (ICA). The contribution of each polluting substance to the PI was determined. The industry database was created and the increase in population and industry, and their densities, were estimated. The results indicated that the temporal pattern of surface water quality is determined by the level of urbanization. The water integrated pollution index (WPI) increased with the passage of time in all the localities: SLG 0.0 to 25.0; SMTL 25.0 to 29.0; SRT 4.0 to 29.0; VA 6.0 to 30.0; T 3.5 to 24.0 and SMA 4.0 to 27.0 from 2010 to 2020, respectively. The correlation coefficients between the five parameters (BOD5, COD, CF, TU and TSS) in the six localities were positive with the population. The values that showed a higher correlation with the population were: SLG (FC 0.86), SMTL (BOD5 0.61, COD 0.89, TSS 0.64) and SRT (TU 0.83), corresponding to highly polluted localities, which generates complex and severe environmental implications due to the unsustainable management of water resources. Achieving the sustainability of water in the watershed is a challenge that should be shared between society and state. This type of research can be a useful tool in making environmental management decisions.