Musculoskeletal injuries (MSK-Is) are a significant health problem for both military and athletic populations. Research indicates that MSK-I is associated with physical fitness; however, the association between specific components of physical fitness and MSK-I in military and athletic populations has not been systematically examined. Our goal was to systematically review the literature to provide a best evidence synthesis on the relationship between components of physical fitness and MSK-I risk in military and civilian athletic populations. This first of 3 manuscripts focuses on cardiorespiratory endurance (CRE). MEDLINE, EBSCO, EMBASE, and the Defense Technical Information Center were searched for original studies published from 1970 through 2015 that examined associations between physical fitness and MSK-I. Forty-nine of 4,229 citations met our inclusion criteria. Primary findings indicate that there is (a) strong evidence that poor performance on a set distance run for time is a predictor for MSK-I risk in both genders; (b) strong evidence that poor performance on timed shuttle runs is a predictor for MSK-I risk in males; (c) moderate evidence in males and limited evidence in females that poor performance on a timed step test is a predictor of MSK-I risk; and (d) limited or insufficient evidence that poor performance on the Cooper run test, maximal and submaximal aerobic graded exercise tests, and the Conconi test are predictors of MSK-I risk in males or females or both. Several measures of CRE are risk factors for training-related MSK-I in military and civilian athletic populations, indicating that CRE may be an important measure for MSK-I risk stratification.