The sensitivity of occupant kinematic and kinetic crash responses to anthropometric and seat adjustment variation was investigated by performing frontal- and side-impact simulations with a family of morphed Human Body Models (HBMs). The HBM family included variations of shape and size, accounting for stature, Body Mass Index (BMI) and sex. A global sensitivity analysis method was developed and applied. Increased BMI was associated with increased spinal and extremity loading in the HBM for all evaluated impacts. Increasing the stature resulted in a consistent increase in lower extremity loading. The fore-aft seat position influenced the head and torso speed relative to the vehicle interior. Furthermore, in high-severity frontal impacts, adjusting the seat position rearwards altered the load path, increasing the HBM pelvic and lumbar spine loading in favour of reducing the lower extremity forces, and vice versa when the seat was positioned forward. The results from this study highlight potential occupant protection challenges and trade-offs, and can be used to enhance protection, considering occupant anthropometric diversity and seat adjustment variation.