Abstract: In recent years, with the widespread application of various explosive weapons, the number of explosion-induced traumatic brain injury (TBI) cases has surged. Current research on explosive blast injuries predominantly focuses on plain environments, while studies on the injury mechanisms, trauma characteristics, and treatment strategies under the special physical and chemical environment of the plateau remain relatively scarce. To elucidate the kinematic response of the human head–neck system under blast loading in low-ambient-pressure conditions, this study employed a high-fidelity physical anthropomorphic surrogate instrumented with overpressure transducers, accelerometers, angular-rate sensors, and a six-axis load cell. Using a shock-tube test platform, experiments were conducted under four ambient-pressure conditions. The results show that, under ambient pressures ranging from 54 kPa to 101 kPa, the free‑field peak overpressure decreases with decreasing ambient pressure (relative to 101 kPa, the peak overpressure at 54 kPa is reduced by approximately 16.03%), and the peak overpressure measured at multiple locations on the head surface also decreases in the low‑pressure range. Meanwhile, translational metrics—such as the peak head center‑of‑gravity (CG) accelerations in the x and z directions and the peak neck forces in the x and z directions—decrease overall with decreasing ambient pressure, whereas rotational metrics—such as the peak head CG angular velocity in the y direction and the peak neck torque in the y direction—increase overall with decreasing ambient pressure. These findings indicate that, under the present test conditions, low ambient pressure exerts opposite effects on the translational and rotational responses of the head–neck system. The study reveals that the injury quantification assessment method established under normothermic and normobaric conditions exhibits applicability bias in high-altitude (hypobaric) environments. This bias arises because high-altitude (hypobaric) conditions can alter human physiological functions (e.g., hypoxia and hypothermia reduce tissue tolerance), and under identical blast loading conditions, injuries tend to be more severe than those at plain levels. Therefore, the method requires calibration and validation under hypobaric conditions. Overall, this study provides a mechanics-based reference for blast-induced injury research and for evaluating the applicability of injury criteria in plateau (low-ambient-pressure) environments.