Antimicrobial resistance (AMR) continues to pose a serious threat to public health worldwide. This has led to the search for novel chemotherapeutic agents capable of acting on multidrug-resistant pathogens. A new series of benzotriazole–1,2,3-triazole hybrid derivatives (Bt1–Bt6) was synthesized through Cu(I)-catalyzed azide–alkyne cycloaddition using propargylated benzotriazole intermediate (2). Structural elucidation for all the synthesized compounds involved IR, ¹H/¹³C NMR spectroscopic analysis which revealed characteristic signals for triazole and functional groups specific to each derivative. Their antibacterial activity was tested against Gram-positive Enterococcus faecalis (ATCC and clinical isolates) and Gram-negative Escherichia coli strains. Two compounds Bt5 and Bt6 showed strongest broad-spectrum activities with MIC values in the range between 0.24–1.24 µg/mL comparable to ciprofloxacin; they also demonstrated very high selectivity together with low cytotoxicity, CC₅₀ =120–135 µg/mL on mammalian cells tested.[89] Compound Bt4 exhibited moderate activity while others were less active thus indicating great role played by incorporation sulfonamide heterocycles into molecule towards antimicrobial potency. Molecular docking research at the 7C7N protein expressed essentially binding affinities correlating with biological activity, Bt5 having the best docking score (−7.4426 kcal·mol⁻¹) supported through several hydrogen bonds and π interactions with key residues Arg76, Ile78, and Pro79. An RMSD value of 0.1324 Å was obtained on redocking the native ligand to validate further that indeed this is a reliable protocol for use in docking exercises such as reported herein where two compounds labeled Bt5 and Bt6 are proposed as potential leads against bacteria due to their demonstrated strong activities besides exhibiting significant differences structurally while still maintaining good safety profiles thereby making them suitable candidates for further optimization along drug development pipelines.