A series of Schiff bases (compounds 1–10) were synthesized by condensing heterocyclic/aromatic aldehydes with heterocyclic/aromatic amines through both, conventional method and microwave-assisted synthesis. The compounds were confirmed by means of IR spectroscopy, Mass spectrometry, 1 H NMR and elemental analyses. The compounds were assayed for antibacterial activity against selected strains of Gram positive, Gram negative bacteria and some fungi by zone inhibition method. Minimum inhibitory concentration (MIC) was also determined for each compound. Reaction times were drastically reduced by microwave-assisted synthesis. MIC was as low as 50 lg/ml exhibited by compounds 2 (against Escherichia coli, Aspergillus niger and Penicillium chrysogenum) and 10 (against Bacillus subtilis). The study presents a series of potential antimicrobial agents through efficient and simple reactions and mild reaction conditions, thereby offering a green chemistry approach.