Background. Fatigue in baseball pitchers is a process linked to lowered physical and mental performance, injury, and changes in kinematics. Numerous studies have associated fatigue with overuse, high ball velocities, lack of rest time, poor mechanics, and degree of self-satisfaction. The aim of this study was to systematically review the literature to identify a theoretical framework for the relationship between outcomes and the manifestation of fatigue on baseball pitching. The synthesized data may identify areas requiring further research. Methodology. This protocol was registered with PROSPERO (ID: CRD42018114194). SPORTDiscus, Medline, PubMed, Cochrane Database of Systematic Reviews, and Google Scholar were searched, using keywords such as fatigue in pitchers and changes in kinematics (e.g. pitching mechanics, valgus elbow torque), performance (e.g. pitch count, pitch type), and injury (e.g. pain, elbow and shoulder soreness). Three reviewers independently screened the articles, selected relevant literature based on abstract eligibility, and assessed the methods described therein for final inclusion. Results. 31,860 articles were screened for eligibility and 25 articles were included for the review. The selected articles included epidemiological, longitudinal, experimental, conference papers, and crossover laboratory studies. Evidence extracted from the 25 studies demonstrates a relationship between fatigue in baseball pitching, and three overarching outcomes: changes in kinematics, a decrease in performance, and an increase in injury risk. Conclusions. Findings show that a co-dependence between changes in kinematics and a decrease in performance, which stems from central and peripheral fatigue, is a contributing factor of injury in baseball pitchers. A large percentage of baseball pitchers exhibit pain or soreness in either their elbow or shoulder, or both at some point in a season. Initially, kinematic changes occur that could maintain performance, but may increase joint and tissue loading. Performance decreased with elevated pitch counts and innings thrown, and pitching further into games or the season. Evidence was found to be consistent across all studies, however, more work is needed in the area of fatigue as an