The escalating presence of per- and polyfluoroalkyl substances (PFAS) in drinking water poses urgent public health concerns, necessitating effective removal. This study presents a groundbreaking approach, using viologen to synthesize covalent organic framework nanospheres: MELEM-COF and MEL-COF. Characterized by highly crystalline features, these nanospheres exhibit exceptional affinity for diverse anionic PFAS compounds, achieving simultaneous removal of multiple contaminants within 30 min. Investigating six anionic PFAS compounds, MEL- and MELEM-COFs achieved 90.0–99.0% removal efficiency. The integrated analysis unveils the synergistic contributions of COF morphology and functional properties to PFAS adsorption. Notably, MELEM-COF, with cationic surfaces, exploits electrostatic and dipole interactions, with a 2500 mg g⁻¹ adsorption capacity—surpassing all reported COFs to date. MELEM-COF exhibits rapid exchange kinetics, reaching equilibrium within 30 min. These findings deepen the understanding of COF materials and promise avenues for refining COF-based adsorption strategies.