This study aimed to investigate the fatiguing characteristics of muscle-tendon units (MTUs) within skeletal muscles during static isometric contraction tasks. The deltoid was selected as the target muscle and three head-related static isometric contraction tasks were designed to activate three heads of the deltoid in different modes. Nine male subjects participated in this study. Surface electromyography (SEMG) signals were collected synchronously from the three heads of the deltoid. The performances of five SEMG parameters, including root mean square (RMS), mean power frequency (MPF), the first coefficient of autoregressive model (ARC1), sample entropy (SE) and Higuchi’s fractal dimension (HFD), in quantification of fatigue, were evaluated in terms of sensitivity to variability ratio (SVR) and consistency firstly. Then, the HFD parameter was selected as the fatigue index for further muscle fatigue analysis. The experimental results demonstrated that the three deltoid heads presented different activation modes during three head-related fatiguing contractions. The fatiguing characteristics of the three heads were found to be task-dependent, and the heads kept in a relatively high activation level were more prone to fatigue. In addition, the differences in fatiguing rate between heads increased with the increase in load. The findings of this study can be helpful in better understanding the underlying neuromuscular control strategies of the central nervous system (CNS). Based on the results of this study, the CNS was thought to control the contraction of the deltoid by taking the three heads as functional units, but a certain synergy among heads might also exist to accomplish a contraction task.