A highly regioselective gold-catalyzed single oxygen transfer reaction, involving internal trifluoromethylated alkynes, pyridine N-oxides, and nitriles, has been developed. The alkyne-attached CF3-moiety functions through an inductive mechanism to direct O-nucleophilic attack specifically to the β-alkyne position. This three-component transformation yields a diverse array of valuable 4-trifluoromethylated oxazoles in high yields (30 examples; up to 96%) under relatively mild gold-catalyzed conditions, demonstrating significant tolerance for various functional groups. The mechanistic experiments indicate the crucial role of the alkyne-attached CF3-group for the formation of the oxazole products. The potential for the facile modification of the directing CF3-group was also demonstrated.