A facile route for the synthesis of 20 new 1,4-disubstituted tetrazolone derivatives from allyl bromides of Baylis–Hillman adducts and various 1-substituted tetrazolones is described. All the synthesized compounds were screened for in vitro antibacterial and antifungal activity. Out of 20 newly synthesized compounds 16 compounds showed very good activity against the Gram-positive bacteria Bacillus subtilis compare to the standard drug ciprofloxacin. The compounds 7b, 7n and 7o showed remarkable activity against both the Gram-positive bacteria B. subtilis and Staphylococcus aureus. Two compounds 7l and 7o showed very good activity against the Gram-negative bacteria Escherichia coli. The compounds, when tested for antifungal activity four compounds— 7b, 7l, 7o and 7s— showed very good activity against the strain Aspergillus niger, whereas seven compounds— 7e, 7g, 7h, 7l, 7o and 7s— display good activity against Candida albicans. Compounds 7b, 7e, 7g, 7l and 7o exhibited very good-to-high activity towards all the strains tested.