Background: Non-contact injuries such as anterior cruciate ligament ruptures often occur during physical load toward the end of a match. This is ascribed to emerging processes due to exercise-induced fatigue. Moreover, non-contact injuries often occur during dynamic actions such as landing or cutting movements. Inter-limb asymmetries are suggested as one possible cause for those injuries based on findings indicating that asymmetries between limbs are associated with a higher injury risk. Hence, assessing inter-limb asymmetry during physical load in the condition of exercise-induced fatigue is warranted to identify potentially relevant precursors for non-contact injuries. Objective: The objective of this study was to overview the current state of evidence concerning the influence of exercise-induced fatigue on inter-limb asymmetries through a systematic review. Methods: A systematic literature search was conducted using the databases Web of Science, Scopus, PubMed, SURF, and SPONET to identify studies that assessed inter-limb asymmetries of healthy people, calculated with an asymmetry equation, before and after, or during a loading protocol. Results: Thirteen studies were included in the systematic review. The loading protocols involved running, race walking, jumping, squatting, soccer, rowing, and combinations of different exercises. Moreover, different tasks/procedures were used to assess inter-limb asymmetries, e.g., squats, single-leg countermovement jumps, gait analysis, or isokinetic strength testing. The results seem to depend on the implemented loading protocol, the tasks/procedures, and the measured parameters. Conclusions: Future research needs more systematization and consistency, assessing the effect of exercise-induced fatigue on inter-limb asymmetries. Moreover, the emergence of inter-limb asymmetries should be regarded in the context of sport-specific movements/tasks. Testing before, after, and during a physical loading protocol is advisable to consider the influence of exercise-induced fatigue on sport-specific tasks and to identify the possible mechanisms underlying load-dependent inter-limb asymmetries with regard to risk of non-contact injury.