The incidence rate of hypertension continues a phenomenal rise and so, there is an ever-increasing demand for the discovery of novel therapeutic agents that have increased efficacy and decreased adverse effects. In these circumstances, benzimidazole was chosen as a potential lead structure and subjected to hologram quantitative structure–activity relationship (HQSAR), comparative molecular field analysis (CoMFA), and comparative molecular similarity indices analysis (CoMSIA). In general, the findings of the QSAR analysis indicate that the LOO cross-validated q2 and r2 values of the HQSAR, CoMFA, and CoMSIA models are respectively 0.983, 0.178, and 0.416, and 0.991, 0.996, and 0.996. HQSAR found that the hydrogen bond donor and acceptor play a big role in how well benzimidazole derivatives work against high blood pressure.