In the present investigation, a series of novel {5-chloro-2-[(3-(substitutedphenyl)-1,2,4-oxadiazol-5-yl)-methoxy]-phenyl}-(phenyl)-methanones (3a-i) have been synthesized from 5-(chloromethyl)-3-substitutedphenyl-1,2,4-oxadiazole (2a-i). The newly synthesized compounds were characterized by IR, NMR (1H and 13C), mass spectral and elemental analysis. The title compounds were investigated for in-vitro qualitative (zone of inhibition) and quantitative (MIC) antibacterial activity by agar cup plate and microtitration methods, respectively. The minimum inhibitory concentration and structure activity relationships (SARs) were evaluated. Amongst the synthesized compounds in this series, {5-chloro-2-[(3-(2,5-difluoro-4-methyl-phenyl)-1,2,4-oxadiazol-5-yl)-methoxy]-phenyl}-(phenyl)-methanone (3d) was found to exhibit significant activity with MICs of 21.5, 22.4, 29.8 and 30.6 microg/mL against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae, respectively.