An efficient one-pot synthesis of 2H-pyranonaphthoquinone was achieved via a palladium-catalyzed C-H bond activation/C-C bond formation/intramolecular Tsuji-Trost reaction cascade. The unprecedented procedure exhibits excellent functional group tolerance, giving the target naphthoquinones in moderate to good isolated yields (40-88%) under mild reaction conditions. Scalable production of the product can make this reaction a method of choice for the synthesis of 2H-pyranonaphthoquinones.