Graphical Abstract Highlight Research 1. Water quality in the Rantau Bayur reach showed marked spatiotemporal heterogeneity under mixed anthropogenic pressure. 2. Ammonia, COD, and WQI were the strongest temporal indicators of deterioration, with November representing the most degraded period. 3. GIS-based mapping identified localized hotspots and confirmed non-uniform spatial deterioration across stations. 4. The Weighted Arithmetic WQI consistently placed the study reach in the poor to very poor category. 5. HCA confirmed that water quality variation was structured by station identity, pressure type, and hydrological connectivity. Abstract Anthropogenic pressures in the Rantau Bayur reach of the Musi River, South Sumatra, Indonesia, are expected to influence local water quality through mixed inputs from sand mining, plantation-related drainage, settlements, coalassociated activities, irrigation-linked channels, and river-based transportation. This study aimed to evaluate the spatio-temporal variability of river water quality under these pressures using physicochemical assessment, the Weighted Arithmetic Water Quality Index (WQI), Geographic Information System, GIS-based spatial analysis, and hierarchical cluster analysis. A total of 99 water samples were collected from five sampling stations between September and November 2025. Water temperature, dissolved oxygen, pH, ammonia, biochemical oxygen demand (BOD), chemical oxygen demand (COD), and dissolved iron were measured and analyzed using descriptive statistics, oneway ANOVA, Tukey’s honestly significant difference test, WQI, GIS-based interpolation, and hierarchical cluster analysis. The results showed that ammonia, COD, and WQI varied significantly among months, with the most deteriorated condition observed in November. BOD and dissolved iron also reached their highest values in the same month, while GIS outputs revealed clear spatial heterogeneity among stations. WQI values remained within the poor to very poor category throughout the study period, indicating persistent degradation of river condition under ongoing anthropogenic influence. Overall, the integration of physicochemical assessment, WQI, GIS, and multivariate clustering provides a coherent short-term appraisal of water quality deterioration in the Rantau Bayur reach and highlights the need for spatially targeted and temporally responsive river management.