A group of new fluoroaniline Schiff bases (3a–3f) were synthesized and structurally characterized by various spectroscopic techniques such as ¹H-NMR, LC-MS and FT-IR spectral studies. All compounds were evaluated for in vitro antibacterial activity. Compounds exhibited good to moderate antibacterial activity. Compound 3f (Zone of Inhibition = 10.08±0.06 µM) was found to be the most active one, and comparable to the standard Streptomycin (IC50 = 15.95±0.08 µM). The compounds having chloro substituent exhibit good membrane damage property against Methicillin-resistant Staphylococcus aureus (MRSA) confirmed by SEM analysis. Structure-activity relationship (SAR) was rationalized by looking at the varying structural features of the molecules.