AbstractWe report a general method for the labeling of both CF3 and CF2H groups in a broad range of chemical settings (aryl, oxide, sulfide). The method utilizes frustrated Lewis pair mediated selective C−F activation to formally substitute fluorine‐19 with fluorine‐18 in a two‐step defluorination/radiofluorination process, and as such can utilize the target compounds as starting materials. The radiotracer precursors can be isolated as stable salts prior to radiofluorination. The method delivers good radiochemical yields and molar activities (up to 35.2±6.5 % non‐decay corrected isolated activity yields and 12.0±1.7 GBq μmol−1 molar activities) and is shown to be applicable to biologically relevant compounds. The ability to utilize the target compound as the starting material and the synthetic simplicity of the method coupled with the ever‐increasing use of CF3 and CF2H groups in pharmaceuticals makes this method attractive for drug and radiotracer development.