Approximately 45% of on-duty related mortalities were due to sudden cardiac death, with many of these fatalities related to cardiovascular disease and overexertion, while performing emergency duties. Therefore, the aim of this systematic review was to determine the association between cardiovascular disease risk factors and cardiorespiratory fitness in firefighters. A literature search of PubMed, SCOPUS, Web of Science, Embase, EBSCOHost, and ScienceDirect was conducted; the Rayyan® intelligent systematic review tool was used to screen and select studies for inclusion. The appraisal tool for cross-sectional studies and the Critical Appraisal Skills Programme toolkit were used for methodological assessment of included studies. Data were analyzed using the Review Manager 5.3 and MedCalc® statistical softwares to determine the effects of obesity (Z = 10.29, p < 0.001) and aging (Z = 4.72, p < 0.001) on cardiorespiratory fitness. Furthermore, there was a significant effect for cardiorespiratory fitness level on systolic blood pressure (Z = 5.94, p < 0.001), diastolic blood pressure (Z = 2.45, p < 0.001), total cholesterol levels (Z = 3.80, p < 0.001), low-density lipoprotein cholesterol (Z = 4.44, p < 0.001), triglycerides (Z = 3.76, p < 0.001) and blood glucose concentration (Z = 4.78, p < 0.001). Cardiovascular disease risk factors and cardiorespiratory fitness were significantly and inversely associated in firefighters. Fire service departments should adopt behavioral intervention strategies to maintain optimum cardiovascular disease risk factor profiles and cardiorespiratory fitness among firefighters to ensure their occupational well-being.