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Background: Muscle synergies are defined as the central nervous system’s organizational structure for movement. Muscle synergies change after muscular fatigue, with certain synergies assuming the primary role to compensate for fatigue within another muscle synergy. Owing to the high eccentric forces imposed upon the external rotators (ie, posterior rotator cuff), pitchers that continue to throw while fatigued are at a significantly higher risk of shoulder and/or elbow injury; however, the neuromuscular compensation strategies of baseball players in response to fatigue are currently unknown. Hypothesis: Players would utilize the same muscle synergy structure following external rotation (ER) fatigue; however, muscle coefficients of nonfatigued muscles would increase (ie, compensate for the external rotators) after fatigue. Study Design: Cross-sectional study conducted in a controlled, laboratory setting. Methods: Nine players from an intercollegiate competitive club baseball team voluntarily participated in this study. Surface electromyography was used on 14 muscles of the glenohumeral and scapulothoracic joints of the dominant arm during a reaching protocol. Players completed a baseline reaching protocol (prefatigue), then an ER fatigue protocol until maximum concentric ER was reduced by 40%, and finally repeated the same reaching protocol (postfatigue). Principal component analysis was used to extract muscle synergies, the variance accounted for (VAF) of each synergy, and muscle coefficients. Prefatigue was compared with postfatigue using paired t tests for all dependent variables. Results: Four muscle synergies were extracted for both pre- and postfatigue. The VAF for the ER/abduction synergy decreased significantly (prefatigue, 34.6%; postfatigue, 32.4%; P = 0.03), showing a decreased reliance on ER/abduction during the reaching task after fatigue. Within synergy 1, the pectoralis major muscle coefficient (−0.489 vs −0.552; P = 0.01; effect size = 1.68) decreased significantly from prefatigue to postfatigue, indicating that the pectoralis major assumed more of an antagonist role during ER/abduction. Within synergy 2 (forward reaching), there were no significant changes in VAF or muscle coefficients observed. For the third synergy, muscle coefficients increased for the serratus anterior ( P = 0.02) and middle deltoid ( P = 0.01), whereas in the fourth synergy, the pectoralis major ( P = 0.01) increased and teres major ( P = 0.01) and biceps brachii ( P = 0.05) muscle coefficients decreased. Conclusion: The decreased VAF of the ER/abduction synergy after fatigue indicate that other muscles within that synergy could not fully compensate to maintain function. Interestingly, the changes in muscle coefficients suggest that players relied less on the internal rotation (IR) synergy and more on the cross-body synergy following fatigue. This may be due to imbalances between ER and IR while maintaining balance between cross-abduction and adduction. Clinical Relevance: Clinicians may consider implementing low-load, high-repetition training programs to develop posterior shoulder endurance and prolong the onset of muscular fatigue.