A four-component, 1,4-addition Ugi reaction using cyclic α,β-unsaturated ketones, carboxylic acids, amines, and isocyanides was developed for the first time. By combining this reaction with Michael addition, nucleophilic substitution, and C-N bond formation reactions, bicyclic and tricyclic scaffolds with pyridinone and quinolinone moieties, two basic units among a variety of natural products and pharmaceuticals, were constructed.