Chlorinated polyfluoroalkyl ether sulfonates (trade name F-53B) has been detected in various environmental matrices, and reported to be equally or more toxic than perfluorooctane sulfonate. Efficient sorptive removal of F-53B from water by two types of layered double hydroxides (LDHs), NO3−-LDH and sodium dodecyl sulfate modified NO3−-LDH (SDS-LDH), was demonstrated in this study. Both LDHs removed F-53B in several minutes and had sorption capacities of over 860 mg/g. SDS-LDH exhibited a greater F-53B uptake than NO3−-LDH under the influence of different solution chemistry, including pH 3-11, or in the presence of competing anions or co-contaminants, primarily due to the higher surface areas and the presence of SDS for SDS-LDH. Batch experiments, structural characterization, molecular dynamics simulations, and density functional theory calculations were combined to explore the sorption mechanisms, which mainly include ion exchange (specifically, O-H⋯O/F hydrogen bond), C-F/Cl⋯H hydrogen bond, and micellar sorption (occurring at high initial F-53B concentrations). Accordingly, we propose to improve the sorption performance of LDHs by increasing their surface areas and modifying LDHs to produce more hydrogen bond sites, as well as exfoliating LDHs into two dimensional nanosheets to eliminate the steric hindrance for the micellar formation of F-53B or other per- and polyfluoroalkyl substances. Display omitted •NO3−-LDH and SDS-LDH showed fast and effective removal of F-53B from water.•Increasing the SBET of LDHs and introducing SDS onto LDHs improved F-53B uptake.•The sorption mechanisms mainly included hydrogen bond and micellar sorption.•The design strategies for future LDHs preparation were proposed.