Abstract <p>This study focuses on the development of novel <i>N</i>-{5-[(3-oxo-3<i>H</i>-benzo[<i>f</i>]chromen-1-yl)methyl]-1,3,4-oxadiazol-2-yl}benzamide derivatives are synthesized by a three-step procedure. First, 2-(3-oxo-3<i>H</i>-benzo[<i>f</i>]chromen-1-yl)acetic acid was synthesized by a modified Pechmann condensation of citric acid with 2-naphthol and then converted into 1-[(5-amino-1,3,4-oxadiazol-2-yl)methyl]-3<i>H</i>-benzo[<i>f</i>]chromen-3-one by reflux with semicarbazide in the presence of POCl₃. Finally, the latter product was reacted with a series of substituted benzoic acids to obtain the target coumarin–oxadiazole hybrids in yields ranging from 60 to 80%. The products were characterized by physical methods (melting point, TLC) and spectral analysis (IR, NMR, and mass spectrometry). In the subsequent antimycobacterial assay, the derivatives with the 4-nitro and 4-chloro substituents in the phenyl ring of the benzamide moieties exhibited the highest inhibitory activity (MIC = 25 µg/mL). Structure–activity relationship analysis was performed to optimize molecular structures for enhanced efficacy.</p>