Assessment of the ecological status of river waters is of great importance for the protection of water resources, their efficient management, and the identification of anthropogenic impacts. The aim of this study was to assess the water quality of selected rivers belonging to the Kura and Araz River basins based on physicochemical and microbiological parameters, as well as to determine the relationships among these parameters using statistical methods. Within the framework of the study, water samples collected from the Lower Kura, Ganjachay, Kurakchay, Tartarchay, Araz River, Hakarichay, Bargushadchay, and Okhchuchay were analyzed for temperature, pH, dissolved oxygen, concentrations of ammonium, nitrite, nitrate, and phosphate ions, total microbiota, saprotrophic bacteria, bacteria involved in the nitrogen cycle, as well as the quantitative abundance of oil- and phenol-oxidizing microorganisms using standard physicochemical and microbiological methods. Pearson correlation analysis, principal component analysis (PCA), and hierarchical cluster analysis (HCA) were applied to evaluate the relationships among the parameters. The obtained results demonstrated that the physicochemical and microbiological parameters of the studied rivers varied both seasonally and among rivers. Higher levels of nutrients and microbiological parameters were observed in the Ganjachay, Araz River, Lower Kura, and Okhchuchay, whereas the Hakarichay, Kurakchay, and Tartarchay were characterized by relatively favorable ecological conditions. A strong positive correlation was identified between total microbiota and saprotrophic bacteria (r = 0.709; p < 0.001). PCA and HCA revealed that the rivers were grouped differently according to nutrient loading, microbiological activity, and the level of anthropogenic impact. The results of the study demonstrate that the integrated application of physicochemical, microbiological, and multivariate statistical approaches provides a reliable framework for the comprehensive assessment of the ecological status of river waters, the identification of river basins associated with ecological risks, and the scientifically based development of long-term monitoring programs.