Perfluorooctanoic acid (PFOA) is an emerging persistent organic pollutant that threatens human health and ecosystems. However, the intricate mechanism of the change in PFOA transport behavior that interacts with FexSy minerals under groundwater-type differences is not clear. To address this knowledge gap, multi-scale experiments and multi-process reaction models were constructed to investigate the underlying mechanisms. The results showed that different groundwater (NO3-, Cl--Na+, SO42-, and HCO3- types) had significant effects on PFOA transport. NO3-, Cl--Na+, SO42-, and HCO3- decreased the retardation effect of PFOA in the FexSy media. Compared to other groundwater types, the adsorption sites of FexSy were the least occupied in the NO3- groundwater. This observation was supported by the least inhabition of λ in FexSy-NO3- interaction system, which demonstrated that more PFOA was in a high reaction zone and electrostatic repulsion was weakest. The surface tension of different ion types in groundwater provided evidence explaining the lowest inhibition in the FexSy-NO3- system. The 2D spatiotemporal evolution results showed that in FexSy with NO3- system, the pollutant flux (6.00 ×10−5 mg·(m2·s)−1) was minimal. The pollutant flux in the SO42- groundwater system was 9.95-fold that in FexSy with the NO3- groundwater. These findings provide theoretical support for understanding the transport and fate of PFOA in FexSy transformations that interact with different types of groundwater.