A highly efficient one-pot domino protocol for the construction of novel indole and coumarin containing pyridine-3-carbonitrile derivatives has been described. The reaction proceeds via one-pot four-component condensation of 3-(1H-indol-3-yl)-3-oxopropanenitrile with various aromatic and aliphatic aldehydes, 3-acetyl-2H-chromenones and ammonium acetate in presence of acetic acid. The present new methodology offers several advantages such as short reaction time, easy experimental work-up, good yields and endures the substrate diversity, operational simplicity under metal-free reaction conditions for formation of C-C/C-N bonds.