Blast-induced traumatic brain injury (bTBI) is a significant health concern in the era of asymmetric warfare. Several mechanisms of bTBI have been proposed in the literature: direct intracranial transmission, skull flexure, thoracic mechanism, cavitation, and head acceleration. The present understanding of bTBI mechanisms and their contributions to brain injury is limited. Specifically, the role of acceleration from the global head motion is often ignored as most of the investigations focus on shorter durations (< 10 ms). This study aims to assess the role of blast-induced global head motion on the brain’s biomechanical response. Using an anatomically accurate, validated finite element human head model, we simulated the blast wave interaction with head-neck complex for 100 ms. These longer duration simulations captured the effects of global head motion and wave propagation within the brain. We observe significant head rotation under the blast loading. Our findings suggest that wave propagation combined with the head translation has a time scale of ~10 ms and governs the volumetric response. In contrast, the head rotation has a timescale of ~100 ms and regulates the brain’s deviatoric response. These results underscore that head rotation plays a critical role even under blast loading. Thus, blast mitigation strategy should focus on mitigating the effects of both wave propagation and global head motion.