Abstract: Objective The key iron mining areas in the middle and lower Yangtze River constitute important hosting units for regional karst-fracture aquifer systems. Clarifying the genesis mechanisms, dominant controlling factors, and resource-environmental effects of groundwater hydrochemistry is of crucial scientific and practical significance for supporting the sustainable utilization of water resources in mining areas and the synergistic enhancement of the Yangtze ecological barrier function. Methods Groundwater samples were systematically collected from key active iron-mining areas. An integrated approach was employed, incorporating multivariate statistics, Piper three-line diagrams, Gibbs diagram interpretation, Phreeqc inverse geochemical modeling, and positive matrix factorization (PMF) models to analyze the characteristics of hydrochemical components, material sources, and their controlling mechanisms at multiple scales. Results Groundwater is predominantly Class-III; Partially, TDS, SO₄²⁻, Fe and Mn marginally exceed background thresholds. The dominant anions are SO₄²⁻ and HCO₃⁻, with cations mainly being Ca²⁺ and Mg²⁺. Hydrochemical facies are mainly SO₄·HCO₃⁻–Ca²⁺·Mg²⁺ and HCO₃⁻·SO₄²⁻–Ca²⁺·Mg²⁺. Rock weathering–dissolution is the principal control; evapoconcentration and precipitation inputs are subordinate. SO₄²⁻, HCO₃⁻, Ca²⁺ and Mg²⁺ share a common source, chiefly derived from oxidative weathering of pyrite and other sulphides and carbonate dissolution, supplemented by cation exchange and minor gypsum dissolution. Mining impacts markedly outweigh agricultural influences. PMF modelling attributes 74.8% of the observed hydrochemical variance to the coupled “sulphide-oxidation/carbonate-dissolution” mechanism. Quantitatively and qualitatively, the groundwater is suitable for diversified industrial and irrigation uses. Conclusions Hydrochemical evolution in the research area is governed by a binary “sulphide-oxidation plus carbonate-dissolution” mechanism, with a pronounced mining overprint. A technical framework integrating real-time water-quality monitoring, source identification and risk-based hierarchical control is recommended to be established so that green-mine construction and ecological security in the middle and lower Yangtze River can be underpinned.