Abstract: Perfluoroalkyl and polyfluoroalkyl substances (PFAS), as emerging contaminants, pose a serious threat to aquatic environments due to their environmental persistence and biological toxicity. However, the transport and retention behaviors of PFAS within river-groundwater interaction zones remain poorly understood. Elucidating the mechanisms governing PFAS migration and retention under fluctuating river stage conditions, as well as identifying the key controlling parameters is therefore essential. Perfluorooctanoic acid (PFOA) was selected as a representative PFAS compound. A one-dimensional PFOA transport model was first developed based on soil column experiments to verify model reliability and to inversely estimate the adsorption coefficient. Subsequently, a two-dimensional river-groundwater cross-sectional model was constructed to simulate PFOA transport within the interaction zone and to evaluate its sensitivity to multiple parameters, including fluctuation amplitude, wavelength, adsorption coefficient, hydraulic conductivity, infiltration recharge coefficient, and porosity. River stage fluctuations induce a pronounced storage effect within the interaction zone, significantly prolonging PFOA residence time and producing an asymmetric transport behavior characterized by “easy entry but difficult release.” Compared with conservative solutes, PFOA exhibits substantially longer retention due to adsorption processes. The adsorption coefficient, fluctuation amplitude, wavelength, and hydraulic conductivity were identified as the dominant factors controlling PFOA migration and retention. An increase in the adsorption coefficient markedly reduces peak concentrations while substantially extending retention time. Greater fluctuation amplitude leads to higher peak concentrations and longer retention, whereas longer wavelengths delay peak arrival and further prolong retention. Higher hydraulic conductivity enhances contaminant transport rates and shortens retention time. These findings provide a theoretical basis for risk assessment and remediation of PFAS contamination in river-groundwater systems subject to seasonal water-level fluctuations.