Selective C-H bond alkynylation toward modular access to material and pharmaceutical molecules is of great desire in modern organic synthesis. Reported herein is Ir(III)-catalyzed regioselective C-H alkynylation of ketones and esters, which is generally applicable for the rapid construction of molecular complexity. This protocol provides a complementary process for conventional alkyne synthesis. Further functionalization of carbonyl-derived material molecules and pharmaceuticals demonstrates the potential synthetic utility of this methodology.