Cervical spine injury resulting from compressive impact loading is a particularly devastating musculoskeletal injury due to the frequency of neurologic involvement. The objective of this research was to investigate the effect of axial eccentricity on the tolerance of the cervical spine. Two functional spinal unit segments (3 adjacent vertebra and their intervening discs and soft-tissues) were dissected from the lower cervical spine of twenty-four human cadaver cervical spines and randomly assigned to one of three loading groups. The eight specimens were tested to failure in compression, compression-flexion, and compression-extension under displacement control on a high-rate MTS load frame. The resulting six-axis loads were measured and evaluated by injury mechanism (group). Statistically distinct (p < 0.01) injury mechanisms, in terms of measured axial eccentricity, were produced by each of the eccentric axial compression inputs (compression-flexion, compression-extension, and compression). The axial force at failure for the compression and compression-extension loading environments were nearly equal and significantly (p < 0.01) larger (4-times) than their counterpart in the compression-flexion group. Failure data were compared with the neck injury criteria (Nij) recently proposed by the NHTSA using the 50th percentile male and 5th percentile female injury reference values. The compression and compression-extension mechanisms produced Nij values near 1.0. The compression-flexion series resulted in significantly lower Nij values at failure (approx. 0.3, p < 0.01). The results of this study provide tolerance data for the cervical spine subjected to different compressive loading environments and may be used to enhance injury reference computations facilitating neck injury prevention.