Herein, we developed a β-cyclodextrin (β-CD)-based polymer crosslinked with tripodal amine to demonstrate the synergetic effects of the superior adsorption of both short- and long-chain per- and polyfluoroalkyl substances (PFASs). Kinetics studies showed rapid adsorption (~100% for nine PFASs at 1 µg L−1, except PFBA, and >86% at 200 µg L−1 individually) within 2 min. Isotherm results showed exceptional adsorption affinity and capacity, with KL = 0.310 ± 0.180 L mg−1, qm = 246.20 ± 14.80 mg g−1 for PFBS, and KL = 0.980 ± 0.260 L mg−1, qm = 587.10 ± 54.50 mg g−1 for PFOS, significantly outperforming traditional activated carbons and resins. Adsorbent performed effectively in PFASs-spiked industrial wastewater with 55–100% removal efficiencies, regardless of the presence of co-contaminants. The adsorption mechanism confirmed the combined role of hydrophobic inclusion within β-CD cavities and electrostatic interactions with amine groups. Overall, this work demonstrates an advanced molecular design strategy for the PFAS-contaminated water and wastewater treatment.