2,5-Bis(pentafluorophenyl)-1,3,4-oxadiazole (FPOx) has been prepared and successfully polymerized with hexafluorobisphenol A (6F-BPA) by means of an aromatic nucleophilic substitution reaction to produce highly fluorinated poly(arylene ether-1,3,4-oxadiazole)s (FPAEOx). The presence of the highly electron-withdrawing oxadiazole (Ox) group in FPOx significantly enhanced the reactivity of the p-fluorine substituents such that the reaction could be completed in only 1-2 h at room temperature in the presence of 4.0 equiv of potassium fluoride (KF). These mild reaction conditions with low reaction temperatures and the use of a mild base effectively prevented side reactions and ensured the formation of polymers with number-average molecular weights up to 64 000 Da free of cross-linking. FPOx itself and this unit in the FPAEOx were found to be capable of selectively binding fluoride anion (F-) with high affinity, and produced new peaks in UV and fluorescence spectra, which are in new regions and well-isolated from the original peaks of FPOx or the polymer. The intensities of these resulting new peaks corresponded to the fluoride concentrations. All these features make the monomer and the polymer potential candidates for fluoride sensory and enable the detection a high reliability and a high sensitivity to the concentration as low as 0.1 ppm. This sensory system also showed a very high selectivity for detecting F-, displaying no response to other tested anions including Cl-, Br-, ClO4-, HSO4-, and PF6-.