Through the prosperity of organofluorine chemistry in modern organic synthesis, perfluorinated organic compounds are now abundant and widely available. Consequently, these substances become attractive starting materials for the production of complex, multifunctional fluorinated molecules. However, the inherent challenges associated with the activation and discrimination of the C-F bonds typically lead to overdefluorination as well as functional group incompatibility. To address these problems, our group utilized a rationally designed organophosphorus reagent that promoted mild and selective manipulation of a single C-F bond in trifluoromethyl and pentafluoroethyl ketones via an interrupted Perkow-type reaction, which allowed the replacement of fluorine with more labile and synthetically versatile congeners such as chlorine, bromine, and iodine. The resulting α-haloperfluoroketones have two reactive units with orthogonal properties that would be suitable for the subsequent structural diversification. DFT calculations identified the favorable P-F interaction as the crucial factor from both thermodynamic and kinetic viewpoints.