The last few decades have shown a dramatic increase in the number of man-made disaster activities resulting in extensive life loss and structural failures. The explosive devices used in these heinous acts result in blast wave loading. Therefore, the present structural engineers require comprehensive expertise to analyze and design blast-resistant structures. The present study aims to develop blast load time history based on the previous research works and demonstrates the effectiveness of base isolation technique such as lead rubber bearings in mitigating the structural responses under the effect of blast loading. Two base-isolated building models systems are analyzed to examine the role of structural control strategies subjected to blast loading. Various isolation parameters are also incorporated in the present investigation in improving the structural performance subjected to this extreme dynamic loading. The study concludes that base isolation is an efficient technique in reducing structural output parameters such as peak storey displacement, storey drift and root mean square absolute acceleration values due to post-blast effects. Energy-based equations are also examined in the study to evaluate the hysteretic energy dissipated by the system subjected to blast loading.