A novel and unique approach for the construction of polysubstituted pyrimido[4,5-b]indoles from 2-(indol-3-yl)naphthoquinones and benzamidines is described. Our strategy, promoted by an inorganic base, involves the ring opening and recyclization of naphthoquinone and produces three nitrogen heterocyclic rings via multiple C-N bond formations in one pot under transition-metal-free conditions.