A multicomponent two-step strategy for the synthesis of polysubstituted pyrrolo[3,2-c]pyridin-4-one derivatives has been described. The reactions can be readily performed by mixing inexpensive starting materials using two-step methods under mild conditions, and the products can be easily obtained from the mother liquid without any further treatment. Moreover, the solid acid catalyst can be circulated at least 6 times without obvious deactivation. Furthermore, a mechanism for the reaction process has been proposed. Overall the bond forming efficiency, the use of green solvent as the reaction medium, recyclability of the solid acid catalyst, easy work-up/purification, and a wide substrate scope make this method highly attractive to assemble heterocyclic scaffolds.