Herein, we report chemoselective trifluoroethylation routes of unmasked 2-arylquinazolin-4(3 H)-ones using mesityl(2,2,2-trifluoroethyl)iodonium triflate at room temperature. Homologous C-, O-, and N-functionalized subclasses are accessed in a straightforward manner with a wide substrate scope. These chemoselective branching events are driven by Pd-catalyzed ortho-selective C-H activation at the pendant aryl ring and base-promoted reactivity modulation of the amide group, leveraging the intrinsic directing capability and competing pronucleophilicity of the quinazolin-4(3 H)-one framework. Furthermore, outstanding photostability of the quinazolin-4(3 H)-one family associated with nonradiative decay is presented.