With the deepening of groundwater resource development and deep mineral resource exploitation, the complexity of fluid seepage and solute transport in fractured rock masses has become increasingly prominent, especially the migration and evolution mechanisms of fracture water chemistry under high-temperature and high-pressure conditions remain unclear. This study explored the laws of sulfate evolution and radon migration under fracture seepage conditions by establishing a multi-factor coupling experimental system, and further deepened the analysis of their internal mechanism of action. Research results showed that an increase in temperature accelerated sulfate generation by increasing the kinetic rate of sulfide oxidation, while it enhancing the thermal motion of radon molecules and significantly increasing the radon migration rate; Increased confining pressure compressed the equivalent hydraulic aperture of fractures, which in turn reduced the reaction interface between sulfides and fluid and increased seepage resistance, thereby resulting in a reduction in sulfate production; The influence of flow rate on sulfate concentration was primarily manifested as a competitive mechanism involving “oxygen supply” and “oxidation time”. Under most operating conditions, the inhibitory effect (caused by increased flow rate shortening fluid residence time) played a dominant role, resulting in a reduction in sulfate concentration; Mineral composition served as the material basis for the migration of sulfate and radon. The sulfate concentration in the fracture seepage fluid of pyrite was much higher than that in limestone, and the RaSO₄ complexes formed by SO₄²⁻ and Ra(radium) led to a significant increase in the concentration of radon generated by decay in the seepage fluid. This study provides important experimental data and theoretical support for numerical simulations of fracture water chemistry and radon migration, as well as environmental risk assessment in deep mining settings.