Herein we have reported a one-pot green methodology for the synthesis of quinoline tethered α-amino ketones. The reaction of arylglyoxal, 2-aminoquinoline, and 4-hydroxy-1-methylquinolin-2(1H)-one/barbituric acid in ethanol under reflux conditions provided the quinoline tethered α-amino ketones. The environmentally benign process, one-pot synthesis, readily available starting materials, short reaction time, easy purification process, good yields of the products, and the presence of several bioactive moieties such as quinolines and α-amino carbonyl in the product are the main advantages of this methodology. All the products were characterized by Fourier transform infrared (FTIR), nuclear magnetic resonance (1H NMR), 13C NMR, and high-resolution mass spectrometry (HRMS). Single-crystal X-ray diffraction (XRD) of one compound was also reported.