A condition-controlled Rh(III)-catalyzed selective synthesis of CF3-substituted indoles and pyrido[2,1-a]isoindoles from 2-arylpyridines and CF3-imidoyl sulfoxonium ylides has been developed. The Cp*Rh(MeCN)3(SbF6)2/HFIP system afforded CF3-substituted indoles via triple C-H activation, while the [Cp*RhCl2]2/MeCN condition selectively furnished CF3-substituted pyrido[2,1-a]isoindoles through C-H [4 + 1] annulation. The notable advantages of this developed method included readily available starting materials, broad substrate scope, and excellent chemoselectivity. Importantly, several selected products showed promising antitumor activities.