This study developed a three-dimensional biomechanical model to investigate the internal loads on the human neck that result from isometrically generated loads resisted by a force on the head. The first goal was to apply the double-optimization (DOPT) method, the EMG-based method, and the EMG assisted optimization (EMGAO) method to the neck model, calculating muscle forces and C4/5 cervical joint loads for each method. The second goal was to compare the results of the different methods, and the third was to determine maximum exertion forces in the cervical spine for isometric contractions. To formulate the EMG-based model, electromyographic signals were collected from 10 male subjects. EMG signals were obtained from 8 sites around the C4/5 level of the neck by surface electrodes, while the subject performed near maximum, isometric exertions. The mean maximum values (±SD) calculated for C4/5 joint compressive forces during peak exertions were 1654 (±308) N in flexion by the EMG method, 1674 (±319) N in flexion by the EMGAO method, and 1208 (±123) N in extension by the DOPT method. In contrast to the DOPT method, the EMG and EMGAO methods showed activation of all the muscles, including the antagonists, and accommodated various load distribution patterns among the agonist muscles during generation of the same magnitude of moments, especially in lateral bending. The EMG and EMGAO methods predicted higher cervical spinal loads than previously published results by the DOPT method. These results may be helpful to engineers and surgeons who are designing and using cervical spine implants and instrumentation.