Background Efficient shoulder movement depends on the ability of central nervous system to integrate sensory information and to create an appropriate motor command. Various daily encountered factors can potentially compromise the execution of the command, such as fatigue. This study explored how fatigue influences shoulder movements during upper limb reaching. Methods Forty healthy participants were randomly assigned to one of two groups: Control or Fatigue Group. All participants completed an upper limb reaching task at baseline and post-experimental, during which they reached four targets located at 90° of shoulder abduction, 90° external rotation at 90° abduction, 120° scaption, and 120° flexion in a virtual reality environment. Following the baseline phase, the Fatigue Group completed a shoulder fatigue protocol, while Controls took a 10-minute break. Thereafter, the reaching task was repeated. Upper limb kinematic (joint angles and excursions) and spatiotemporal (speed and accuracy) data were collected during the reaching task. Electromyographic activity of the anterior and middle deltoids were also collected to characterize fatigue. Two-way repeated-measures ANOVA were performed to determine the effects of Time, Group and of the interaction between these factors. Results The Fatigue group showed decreased mean median power frequency and increased electromyographic amplitudes of the anterior deltoid (p < 0.05) following the fatigue protocol. Less glenohumeral elevation, increased trunk flexion and rotation and sternoclavicular elevation were also observed in the Fatigue group (Group x Time interaction, p < 0.05). The Control group improved their movement speed and accuracy in post-experimental phase, while the Fatigue group showed a decrease of movement speed and no accuracy improvement (Group x Time interaction, p < 0.05). Conclusion In a fatigued state, changes in movement strategy were observed during the reaching task, including increased trunk and sternoclavicular movements and less glenohumeral movement. Performance was altered as shown by the lack of accuracy improvement over time and a decrease in movement speed in the Fatigue group.