The investigation presents a straightforward synthesis of fourteen novel 2-amino-4-aryl-3-(4-fluorophenyl)-4,6,7,8-tetrahydroquinolin-5(1H)-one derivatives via a catalyst-free one-pot four-component cyclocondensation reaction of dimedone, various substituted benzaldehydes, 4-fluorophenylacetonitrile, and ammonium acetate in water under the influence of ultrasound. In comparison with the literature methods, our approach is more effective and offers several advantages, such as safe handling, excellent yields, shorter reaction time, and a simple workup procedure. All the synthesized derivatives were obtained in 87-97% yields and were characterized by IR, H-1, C-13 NMR, and ESI mass spectra and elemental analysis.