Water quality is one of the determinants of human well-being and ecosystem health. The increasing deterioration of its quality is one of the most widespread and worrisome environmental problems. In this context, the dynamics of water quality of the Cunas River in rural and urban areas in the central region of Peru during 2017–2019 was evaluated. A total of 168 water samples were collected from 56 sampling sites and nine physicochemical parameters and three heavy metals were determined. The results obtained reveal that the physicochemical parameters did not exceed the environmental quality standards for water, except BOD5 and Fe. Cluster analysis generated three statistically significant clusters based on similar water quality characteristics and the year of study. Group 1 consisted of sectors S6 (2019) and S7 (2017–2019), group 2 consisted of S5 (2017–2019) and S6 (2017 and 2018), and group 3 consisted of S1, S2, S3 and S4 (2017–2019). The PCA generated three main factors with eigenvalues >1, explaining 76.45% of the total variance. PC1, PC2 and PC3 explained 57.6%, 10.08% and 8.70%, respectively. Water quality according to the WQI in the rural sectors was qualified as good quality water and in 67% of the urban sectors, as poor quality water.