Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that are challenging to remove from contaminated sources. Ion-exchange (IEX) resins that contain ammonium groups are commonly used for PFAS removal, relying on electrostatic interactions to capture anionic PFAS. Commercially available IEX products contain a variety of substituents on the ammonium cations, but little is known regarding the structure–property relationships of cation identification and PFAS removal. In this study, we prepared a series of IEX resins that have different charged segments to investigate their role in PFAS removal efficiency and capacity. To be more specific, polystyrene-based IEX resins were prepared using pentafluorostyrene, vinylbenzene chloride, and divinylbenzene [poly(FVD)], followed by quaternization with trimethylamine (TMA), tributylamine, triethylamine, or dimethylaminoethanol. Among all resins, the TMA+-containing IEX resins demonstrated the highest PFAS removal capacity, rapid sorption kinetics, and good regeneration capability. We hypothesize that the superior performance of poly(FVD)-TMA+ resin is due to the more efficient quaternization using TMA as well as its low dissociation energy with Cl– and high exposure of cationic groups, leading to easier replacement by PFAS molecules. In addition, poly(FVD)-TMA+ performs significantly better for PFAS removal from landfill leachate and effluent lagoon natural water masteries compared to commercially available IEX resins like PFA694E and PSR2+. Overall, this study provides crucial design criteria for charged groups for preparing efficient PFAS sorbents with enhanced removal performance.