A number of pre-designed benzoxepine-1,2,3-triazole hybrids were synthesized for the first time using a Cu-catalyzed azide–alkyne cycloaddition (CuAAC) strategy. Thus, a remarkably rapid click reaction of 7,9-disubstituted (Z)-4-(azidomethyl)-5-chloro-2,3-dihydrobenzo[b]oxepine with terminal alkynes at room temperature in DMF afforded twenty novel (Z)-1-((5-chloro-2,3-dihydrobenzo[b]oxepin-4-yl)methyl)-1H-1,2,3-triazole derivatives in good to excellent yields. All these compounds were tested for their antibacterial properties against four strains of bacterial microorganisms including two Gram-positive and two Gram-negative species. Some of them showed better activity against Gram-negative bacteria (Escherichia coli) over the Gram-positive strains, indicating the special effectiveness of the present class of compounds towards Gram-negative species. These compounds also showed cytotoxicity against lung and colon cancer cell lines.