Many biologically active nicotinonitriles have been reported to date. Consequently, the development of synthetic methods for multiply arylated/alkylated nicotinonitriles remains a sought-after field of research. In the present work, a new synthetic strategy for multi-substituted nicotinonitriles was provided. A FeCl3-promoted condensation-cyclization reaction of an enamino nitrile and α,β-unsaturated ketones efficiently proceeded with a wide range of substrates. It is noteworthy that this method facilitated the access to fully- and differently substituted nicotinonitriles including tetra-arylated nicotinonitriles in only three steps. Using the functionality of the cyano group, the copper-catalyzed annulation reaction of the nicotinonitrile was achieved to yield benzo[c][2,7]naphthyridin-5(6H)-one.