In the present research work, the motto was to develop new chemical entities as potential antimicrobial agent. The recent expansion of antimicrobial drug research has occurred because there is a critical need for new antimicrobial agents to treat these life threatening invasive infections. In the present study three series of new substituted pyrazolone derivatives (3i, 7a-l) were synthesized by the condensation reaction of pyrazolones with various substituted aromatic aldehyde (5), further intermediate reacts with a benzyl chloride. These newly synthesized compounds were characterized by IR spectra. New compounds were screened for their antimicrobial studies against S. aureus, B. subtilis, E. coli and P.aeruginosa, C.albicans, A.niger. The results revealed that compounds substituent showed significant antibacterial activity against all tested microorganisms and fungi as compared to the standard drug Streptomycin, fluconazole.