Objective To investigate the effect of active muscle response on mechanical responses and injuries of human neck under high Gx loading. Methods A refined finite element model of the head and neck with active muscle response was established and validated based on the existing post-crash volunteer experiments. The effects of active muscle action on the kinematic and biomechanical responses of the neck were investigated under different G-value loads and at each tilting angle using this model. Results The stress distribution of vertebrae under high Gx load was dispersed from C4–7 to the whole vertebrae, and the active muscle action reduced the stress change, and the effect was significant in the case of 8 G acceleration, which reduced the peak vertebral bone stress by 23.6% and 11.6%, and the peak intervertebral disc stress by 42.3% and 63.4% under 8 G and 10 G conditions, respectively. The maximum stress difference of 34.3 MPa was achieved by the active muscle action at 15° backward tilting. Conclusions The neck showed better stability by the active muscle action under the impact of high Gx load. At different tilting angles, the active muscle action was more obvious in the backward tilting posture compared with the forward tilting and upright seated postures, and the backward tilting posture was safer to meet the impact when the same active muscle action was applied. The results can provide a reference for the subsequent studies related to the neck injury.