In the present study, a convenient and efficient synthetic route was adopted for the preparation of quinoline-linked chalcone derivatives with potential biological importance. N-methylacetanilide was initially synthesized through acetylation of N methylaniline using acetic anhydride and glacial acetic acid. The synthesized intermediate was then subjected to the Vilsmeier–Haack reaction to obtain 1,2- dihydro-1-methyl-2-oxoquinoline-3-carbaldehyde. Further, the aldehyde intermediate was condensed with various substituted acetophenones through Claisen–Schmidt condensation in the presence of piperidine and ethanol to yield quinoline chalcone derivatives. Structural characterization was performed using FT-IR, ¹H NMR, ¹³C NMR and LC-MS spectral techniques, which confirmed the successful formation of the target compounds. Preliminary biological evaluation suggested promising antibacterial potential for the synthesized derivatives. The study highlights the significance of quinoline-based chalcones as promising scaffolds for future medicinal and pharmaceutical research.