The removal of toxic poly− and perfluoroalkyl substances (PFAS) as persistent pollutants from wastewater is imperative but challenging for water remediation. Many adsorbents including activated carbon, biochar, and clay minerals have been investigated for PFAS removal, but most of these materials are faced with high cost or/and low efficiency. The use of metal−organic frameworks (MOFs) as sorbents is attractive for efficient removal of PFAS due to their tailor-made structures and high surface areas. Herein, we synthesized, characterized a water stable Zr−based porphyrinic MOF (PCN−224) with cooperative adsorption domains, and demonstrated its excellent capture performance toward perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS) and perfluorobutane sulfonate (PFBS). PCN−224 has maximum uptake capacities of 963, 517, and 395 mg g−1 for PFOS, PFHxS, and PFBS, respectively, which are much higher than that of granular activated carbon. Moreover, coexistent anions (Cl−, SO42−) and humic acid have negligible effects on PFOS adsorption. The excellent adsorption performance of PCN−224 toward PFOS is due to the orthogonal cationic channel pores with a diameter of 1.9 nm, hydrophobic porphyrin units, and the Zr6 clusters with acidic sites. PCN−224 can be readily regenerated and reused. This work highlights the potential of MOFs with multiple adsorption domains for water remediation.