Neck pain and injuries are growing healthcare burdens with women having a higher incidence rate and poorer treatment outcomes than males. A better understanding of sex differences in neck biomechanics, foundational for more targeted, effective prevention or treatment strategies, calls for more advanced subject-specific musculoskeletal modeling. Current neck musculoskeletal models are based on generic anatomy, lack subject specificity beyond anthropometric scaling, and are unable to accurately reproduce neck strengths exhibited in vivo without arbitrary muscle force scaling factors or residual torque actuators. In this work, subject-specific neck musculoskeletal models of 23 individuals (11 male, 12 female) were constructed by integrating multi-modality imaging and biomechanical measurements. Each model simulated maximal voluntary neck static exertions in three postures: neck flexion in a neutral posture, flexion in a 40° extended posture, and extension in a 40° flexed posture. Quantitative model validation showed close agreement between model-predicted muscle activation and EMG measurement. The models unveiled that (1) males have greater moment arms in one flexor muscle group and five extensor muscle groups, (2) females exhibited higher cervical spinal compression per unit exertion force in the flexed posture, and (3) the variability of compression force was much greater in females in all three exertions but most notably in the extension with a flexed “dropped head” position. These insights illuminated a plausible pathway from sex differences in neck biomechanics to sex disparities in the risk and prevalence of neck pain.