We describe an efficient one-step synthesis of pyrrolo[3,4-c]quinolinedione derivatives using ethylenediamine diacetate (EDDA)-catalyzed cascade reactions of isatins and β-ketoamides. It is the first direct conversion of isatins to pyrrolo[3,4-c]quinolinedione derivatives via C–N bond cleavage and isatin ring expansion. Furthermore, this reaction provides a one-step synthetic route for the production of biologically interesting complex molecules that are generally prepared using multi-step reactions.