Despite that some types of eating disorders (ED) and substance use disorders (SUD) are among the deadliest of psychiatric disorders, no study has yet examined the effects of different constellations of ED and SUD comorbidity on mortality. Thus, we deemed it necessary to examine the contribution of alcohol use disorders (AUD) and other SUD to raised mortality across the full spectrum of ED, including anorexia nervosa (AN), bulimia nervosa (BN), and unspecified ED (USED). Our register-based, retrospective cohort study showed that SUD involving alcohol, cannabis, and hard drugs had an additive effect on all-cause mortality risk in a large sample of patients with AN, BN, or USED. The pattern of risk differed across the ED types. AN and USED patients both with and without SUD exhibited an increased risk compared to controls without SUD, but the risk was much higher in those with SUD in particular hard drugs abuse/dependence. For patients with BN, only those with SUD exhibited an increased risk, and hard drugs abuse/dependence was associated with the greatest risk. These findings highlight the importance of focusing on the prevention and treatment of SUD in order to reduce excess mortality in ED patients. This is particularly relevant for AN patients who abuse hard drugs since they were found to be the most susceptible to premature death. Interestingly, the driving factor behind mortality in BN patients appears to be SUD and, thus, the prevention and treatment of SUD would go a long way towards reducing mortality in BN.