The emerging classes of perfluorinated alkyl substances (PFAS) (e.g., Perfluorobutanoic acid (PFBA), perfluorobutane sulfonic acid (PFBS), GenX, ADONA, and F–53B) are persistent and recalcitrant to removal by conventional treatment techniques. Herein, we report on poly (N-[3-(dimethylamino)propyl]acrylamide, methyl chloride quaternary, DMAPAA-Q) hydrogel matrix as an effective sorbent for sequestering PFAS from different water matrices. The selective removal of 16 PFAS from different classes using DMAPAA-Q polymer was confirmed in surface waters and treated wastewater at environmentally relevant concentration (i.e., <1000 ng/L). The results showed fast removal kinetics with equilibrium time of 60–120 min and a higher removal of sulfonated than carboxylic PFAS, regardless of their chain lengths. These observations were in agreement with adsorption energy calculations of short- and long-chain PFAS on poly DMAPAA-Q hydrogel using density functional theory (DFT). No desorption was observed when the experimental time was extended to 24 h, which gives an added advantage of poly DMAPAA-Q hydrogel over previously reported adsorbents in the literature. In addition, the removal efficiency was not affected under a varying pH range of 4–10. The impact of background anions on PFAS removal by poly DMAPAA-Q hydrogel was tested and found to follow an order of SO₄²⁻ > Cl⁻ > NO₃⁻. The performance of poly DMAPAA-Q hydrogel was maintained in six consecutive adsorption/regeneration cycles to remove PFAS. The unique fast kinetics and high adsorption activity of poly DMAPAA-Q hydrogel towards PFAS exhibits a great potential for being a promising material for PFAS control.