A series of 3-{5-[(E)-(substituted benzylidene) amino]-1,3,4-oxadiazol-2-yl}-2H-chromen-2-ones (4a–r) were synthesized by the reaction of 3-(5-amino]-1,3,4-oxadiazol-2-yl}-2H-chromen-2-one with different substituted benzaldehydes to form Schiff bases of coumarin-incorporated 1,3,4-oxadiazole derivatives. The structures of the compounds were confirmed on the basis of their elemental analysis and spectral data. The compounds were screened against bacterial strains Staphylococcus aureus NCTC (10418), Escherichia coli NCTC (6571), and fungal strain Candida albicans ATCC (10231). Ciprofloxacin and Ketoconazole were used as standards. The test compounds and standards were evaluated at 100 lg/ml concentration. DMF (N,N-dimethylformamide) was used as solvent and control. Most of the synthesized compounds possess significant antimicrobial activity. Compound (4m) without any substitution of the phenyl ring which is attached to 1,3,4-oxadiazole moiety showed highly significant in vitro growth inhibition against S. aureus and E. coli, while as compound (4g) with para N(CH3)2 showed highly significant in vitro growth inhibition against C. albicans.