An efficient and straightforward protocol for the assembly of the pharmaceutically and biologically valuable oxazole skeleton is achieved for the first time from readily available simple arenes and functionalized aliphatic nitriles. This transformation involves palladium-catalyzed C–H activation, carbopalladation and a tandem annulation sequence in one pot. Notably, the reaction proceeds efficiently under redox-neutral conditions, and exhibits high atom-economy. Deuterium-labeling experiments suggested that C–H bond cleavage of the simple arenes might be the rate-determining step.