The objective of the present study was to determine the instantaneous moment arms of 18 major muscle sub-regions crossing the glenohumeral joint during coronal-plane abduction and sagittal-plane flexion. Muscle moment-arm data for sub-regions of the shoulder musculature during humeral elevation are currently not available. The tendon-excursion method was used to measure instantaneous muscle moment arms in eight entire upper-extremity cadaver specimens. Significant differences in moment arms were reported across sub-regions of the deltoid, pectoralis major, latissimus dorsi, subscapularis, infraspinatus and supraspinatus (P < 0.01). The most effective abductors were the middle and anterior deltoid, whereas the most effective adductors were the teres major, middle and inferior latissimus dorsi (lumbar vertebrae and iliac crest fibers, respectively), and middle and inferior pectoralis major (sternal and lower-costal fibers, respectively). In flexion, the superior pectoralis major (clavicular fibers), anterior and posterior supraspinatus, and anterior deltoid were the most effective flexors, whereas the teres major and posterior deltoid had the largest extensor moment arms. Division of multi-pennate shoulder muscles of broad origins into sub-regions highlighted distinct functional differences across those sub-regions. Most significantly, we found that the superior sub-region of the pectoralis major had the capacity to exert substantial torque in flexion, whereas the middle and inferior sub-regions tended to behave as a stabilizer and extensor, respectively. Knowledge of moment arm differences between muscle sub-regions may assist in identifying the functional effects of muscle sub-region tears, assist surgeons in planning tendon reconstructive surgery, and aid in the development and validation of biomechanical computer models used in implant design.