Motor vehicle collisions (MVCs) are a leading cause of traumatic injury to the cervical spine, with the activity of the cervical muscles influencing occupant kinematics and injury risk in response to dynamic loading. The purpose of this study was to investigate the effect of muscle activation timing, level, and coordination of muscle groups on global and local tissue-level response. A model of the cervical spine with active musculature was developed and evaluated for performance in a 15 g frontal impact. Furthermore, a parametric study was conducted to investigate the correlations between muscle activation parameters, global injury metrics, and local tissue loads. Early muscle activation was found to reduce linear head accelerations and head rotation, while increasing loading to the upper cervical ligaments. Furthermore, greater maximum muscle force primarily reduced posterior ligaments loads, particularly for the upper cervical spine. Upper cervical ligament forces were strongly correlated with HIC and NIJ injury risk measures, while posterior ligaments had a strong correlation with HIC. The alar and transverse ligaments, which have clinical significance for injury risk, were specifically identified as strongly correlated with activation timing and maximum muscle force as well as HIC and NIJ. Therefore, this study provided further insight into the effect of muscle activation and timing on injury risk with investigation at a global as well as localized tissue level. In this study, muscle activation parameters were further highlighted as important parameters for future modeling efforts focused on injury risk mitigation in automotive collisions.