This study investigated the degradation of perfluorooctanesulfonate (PFOS) in a reactive electrochemical membrane (REM) system in which a porous Magnéli phase titanium suboxide ceramic membrane served simultaneously as the anode and the membrane. Near complete removal (98.30 ± 0.51%) of PFOS was achieved under a cross-flow filtration mode at the anodic potential of 3.15 V vs standard hydrogen electrode (SHE). PFOS removal efficiency during the REM operation is much greater than that of the batch operation mode under the same anodic potential. A systematic reaction rate analysis in combination with electrochemical characterizations quantitatively elucidated the enhancement of PFOS removal in REM operation in relation to the increased electroactive surface area and improved interphase mass transfer. PFOS appeared to undergo rapid mineralization to CO2 and F-, with only trace levels of short-chain perfluorocarboxylic acids (PFCAs, C4-C8) identified as intermediate products. Density functional theory (DFT) simulations and experiments involving free radical scavengers indicated that PFOS degradation was initiated by direct electron transfer (DET) on anode to yield PFOS free radicals (PFOS•), which further react with hydroxyl radicals that were generated by water oxidation and adsorbed on the anode surface (•OHads). The attack of •OHads is essential to PFOS degradation, because, otherwise, PFOS• may react with water and revert to PFOS.