This work summarizes the results of the synthesis of imidazo[1,2-a]pyrazine-linked 1,2,3-triazole derivatives and provides evidence for the importance of this motif as a lead structure for novel drug discovery. The novel synthetic approach to imidazo[1,2-a]pyrazin-1,2,3-triazole derivatives, developed in this work, is based on the click chemistry approach. Nine novel hybrid compounds were synthesized and characterized by IR and H-1 and C-13 NMR spectroscopy, mass spectrometry, and elemental analysis. The synthesized products were tested for antimicrobial activity against E. coli, P. aeruginosa, E. aerogenes, B. megaterium, S. aureus, and B. subtilis bacterial strains and A. niger, and A. flavus fungal strains. The antimicrobial activity was evaluated in terms of the minimum inhibitory concentration (MIC). Some of the test compounds showed a high activity antibacterial and antifungal activity.