Fatigue in emergency first responders (EFRs) is known to affect performance abilities and safety outcomes for both patients and EFRs. The primary aim of this review was to determine the main contributors to occupation-induced fatigue in EFRs and its subsequent impacts. Following the PRIMSA checklist, academic databases (Medline, Embase, CINAHL, and SPORTDiscus) were searched using key terms with results subjected to inclusion and exclusion criteria. Populations of interest were firefighters, paramedics, or emergency call centre personnel. Of the 5633 records identified, 43 studies, which reported on 186 unique measures from a total population of 6373 participants, informed the review. Synthesis revealed fatigue was caused by lack of sleep during the shift and consistent poor sleep quality which negatively impacted cognitive function, alertness, and physical and mental health while increasing safety-compromising behaviours and injuries. Both subjective and objective assessments of fatigue are necessary for effective risk management in EFRs. EFRs that are consistently fatigued are at a greater risk of poor physical and mental health, reduced cognitive function, and increased injuries. No studies reported on fatigue in emergency call centre personnel, highlighting a literature gap. Funding was provided by the Australian Capital Territory Emergency Services Agency. Preregistration was filed in OSF: osf.io/26f3s.