This study evaluates whether existing long-term monitoring data are sufficient to distinguish natural background concentrations from anthropogenic influences on chemical river water quality in Lake Sevan basin. A comprehensive dataset covering physicochemical parameters, nutrients, and trace metals was analyzed for nine major tributaries with different geological settings and land-use characteristics. Multivariate statistical analysis was applied to identify baseline conditions and deviations attributable to human activities. The results indicate that water chemistry is primarily controlled by lithology and hydrological regime, particularly in minimally impacted headwater regions. In contrast, elevated concentrations of nutrients (e.g., nitrate and phosphate) and selected trace elements were associated with agricultural runoff, urban discharge, and localized industrial inputs. Spatial patterns reveal clear gradients of increasing anthropogenic impact downstream and in densely populated sub-basins. The study also demonstrates that, while the current monitoring network is suitable for assessing the overall chemical status of rivers, it is less effective in defining natural background levels and quantifying individual pollution sources due to limited upstream reference conditions. Overall, this approach provides a scientific basis for improved water quality management and policy implementation in the Lake Sevan basin. The findings highlight the importance of integrating long-term monitoring data with statistical tools to support sustainable watershed management in vulnerable catchments.