Medicinal chemistry highly values the benzimidazole scaffold as a pharmacophore owing to its versatile range of biological functions. In the present study, 17 derivatives of 2‐aryl‐N1‐arylacetamido benzimidazoles 3(a–q) were synthesized by nucleophilic substitution reactions between different 2‐chloro‐N‐(aryl)‐acetamides 2(a–q) and 2‐(4‐chlorophenyl)‐1H‐benzo[d]imidazole (1) in N, N‐dimethylformamide, and evaluated for in vitro anti‐HIV and antifungal activities. Of these derivatives, compounds 3 a, 3 b, 3 i, and 3 n showed moderate inhibitory efficacy against HIV‐1 RT, whereas the remaining compounds showed negligible activity compared to the standard drug efavirenz. In contrast, most of the test compounds demonstrated significant efficacy against fungal strains such as Candida albicans and Aspergillus niger. Compounds 3 a, 3 f, 3 m, and 3 n were the most effective antifungal agents. We applied computational approaches to rationalize the potency of the newly synthesized inhibitors.