An effective and accessible synthesis of alkoxy arylnicotinonitriles was achieved via a four-component reaction of 4-hydroxybenzaldehyde, acetophenones, and malononitrile in the presence of sodium alkoxide. The synthesized alkoxy arylnicotinonitrile derivatives containing pyridine moiety were predestined as inhibitors for C1018-steel (CS) corrosion in 1.0 M HCl using Tafel polarization and electrochemical impedance spectroscopy methods in the temperature range of 20–50 °C. Tafel polarization plots were demonstrated that the arylnicotinonitriles behave as typical inhibitors of the mixed type. They have also suppressed the CS corrosion at a lower inhibitor concentration and accomplished an inhibition capacity ranged from 87.6 to 98.2% in 0.7 mM. Their adsorption on the CS interface follows the isotherm model of Langmuir, and they include both chemisorption and physisorption mechanisms, with a preference of chemisorption. The morphology of the CS surface was examined utilizing Fourier transform infrared spectroscopy and field-emission scanning electron microscopy. Moreover, density functional theory calculations confirm the empirical findings and the adsorption of arylnicotinonitrile derivatives on the CS interface.