The current research article describes synthesis of biologically important Imidazo[2,1-b] [1,3,4]thiadiazole derivatives bearing pharmacologically important Isoxazolone moiety. Initially the required key intermediates 5-formyl imidazo[2,1-b][1,3,4]thiadiazoles were prepared by Vilsmeier Haack reaction in DMF and POCl3 mixture. Subsequently the desired Isoxazolone derivatives were prepared by Knoevenagel condensation. The synthesized compounds were characterized by 1H NMR, 13C NMR, and mass spectral studies. All the compounds were screened for their antibacterial activities. Some of the compounds displayed very good antibacterial activity.