Muscle fatigue can cause people to change their movement patterns and these changes could contribute to acute or overuse injuries. However, these effects depend on which muscles are fatigued. The purpose of this study was to determine the differential effects of proximal and distal upper extremity muscle fatigue on repetitive movements. Fourteen subjects completed a repetitive ratcheting task before and after a fatigue protocol on separate days. The fatigue protocol either fatigued the proximal (shoulder flexor) or distal (finger flexor) muscles. Pre/Post changes in trunk, shoulder, elbow, and wrist kinematics were compared to determine how proximal and distal fatigue affected multi-joint movement patterns and variability. Proximal fatigue caused a significant increase (7°, p < 0.005) in trunk lean and velocity, reduced humeral elevation (11°, p < 0.005), and increased elbow flexion (4°, p < 0.01). In contrast, distal fatigue caused small but significant changes in trunk angles (2°, p < 0.05), increased velocity of wrench movement relative to the hand (17°/s, p < 0.001), and earlier wrist extension (4%, p < 0.005). Movement variability increased at proximal joints but not distal joints after both fatigue protocols (p < 0.05). Varying movements at proximal joints may help people adapt to fatigue at either proximal or distal joints. The identified differences between proximal and distal muscle fatigue adaptations could facilitate risk assessment of occupational tasks.