Novel triazole and pyrimidine derivatives were efficiently evaluated for antibacterial activity against Mycobacterium tuberculosis strain H37Rv by the Resazurin MIC assay. This new structural class of compounds showed high activity against the bacilli. The activity depends on the substituent's present in chalcones of 1,2,4-triazole and pyrimidine core. Compounds having a 4-ClC6H4, 3-NO2C6H4, 2,4-MeOC6H4, 2-ClC6H4, 4-MeOC6H4 and 4-BrC6H4 group as the substituent on pyrimidine and triazole ring were active. The highest activity was registered for compounds having 4-ClC6H4, 3-NO2C6H4 and 2,4-MeOC6H4 as substituents. The new compounds showed high potency and promising antitubercular activity and should be regarded as new hits for further development as a novel class of Anti-Mycobacterium tuberculosis agents.