A sulfur‐promoted three‐component reaction of isatoic anhydride, primary aliphatic or aromatic amines, and acetophenones leading to densely substituted 3‐substituted 2‐aroylquinazolin‐4(3H)‐ones is reported. The key step involves a cascade reaction of selective oxidation of the methyl group of the acetophenones, followed by a condensation with anthranilamides. The scope of the reaction is applicable to the synthesis of tryptanthrin and various 3‐unsubstituted 2‐aroylquinazolin‐4(3H)‐ones.magnified image