2-(4-Amino-3-(4-chlorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-N'-[(2,6-dihalogenophenyl)methylene]acetohydrazides (3a, b) was obtained via the formation of 2-(4-amino-3-(4-chlorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl) acetohydrazide (2), which was obtained starting from 4-amino-5-(4-chlorophenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one (1) in 2 steps. 2-{[ 4-amino-3-(4-chlorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl] acetyl}-N-phenylhydra-zine carbothioamide (4), which was prepared starting from 2, was converted to the corresponding 1,3,4-thiadiazole derivative (5) in acidic media. Moreover, the basic treatment of 4 resulted in the formation of 4-amino-5-(4-chlorophenyl)-2-[(4-phenyl-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl) methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (7). The reactions of compounds 5 and 7 with methyl iodide in the presence of sodium ethoxide afforded the corresponding N-methyl (6) and S-methyl (8) derivatives, respectively. The synthesis of Mannich bases (10a and 10b) was performed from the reaction of 7 with morpholine or piperazine in the presence of formaldehyde. All the newly synthesized compounds were screened for their antimicrobial activity. The antimicrobial activity study revealed that compounds 3a, 3b, and 5 showed good antimicrobial activities against the test microorganisms as compared with ampicillin.