Objective To analyze the neck muscle activity during head flexion and explore the cause of muscle fatigue in human head and neck. Methods A musculoskeletal model of head neck complex was established based on AnyBody software platform, and the muscle strengths during head flexion were simulated according to the input data measured by Vicon motion capture system, which were validated with the literature data. Results The neck muscles played a major role during head flexion. The force assignment mode among muscles was different during 45% and 75% flexion process. The integral of muscle strengths on flexion angle WM could reflect the muscle fatigue to some extent. Since the largest WM was found in the semispinalis cervicis and multifidus muscles during head flexion, it may indicate that those muscles have the easy tendency to be fatigue. Conclusions The musculoskeletal model established in this paper can provide a technical support for the exploration of neck fatigue mechanism.