<p>Karst water serves as a crucial source of water supply in many regions worldwide, yet it remains environmentally sensitive and highly vulnerable to pollution, especially from mining activities. Understanding the spatial–temporal variations in water quality and identifying the key geochemical processes in mining-impacted karst rivers are essential for ensuring regional water security and effective environmental management. This study undertakes a karst river affected by acid mine drainage (AMD), where typical mining activities generated wastewater, using a combination of Integrated Pollution Index (P), irrigation suitability assessment, health risk assessment, and multivariate statistical analysis to elucidate the impact of mining on water quality dynamics. The results show that seasonal variation of P and irrigation suitability follows the trend: dry season &gt; flat season &gt; wet season, but health risk assessments did not show significant differences in time. Spatially, streams influenced by upstream AMD exhibited higher P and lower irrigation suitability, indicating poor water quality unsuitable for both drinking and agricultural use. In contrast, downstream water quality improved due to dilution processes. Health risk assessments identified Mn as the primary non-carcinogenic risk factor in the study area. Multivariate statistical analysis revealed that water quality variations were predominantly controlled by pH, TN, NH₃-N, SO₄²⁻, Ca²⁺, Mg²⁺, and heavy metals, all of which are closely associated with enhanced mineral weathering impacted by mining activities. These findings provide a scientific basis for targeted environmental policy-making and sustainable management strategies aimed at protecting the ecological integrity of karst river systems under mining pressure.</p>