Individuals with schizophrenia or substance use disorder have a substantially increased mortality compared to the general population. Despite a high and probably increasing prevalence of comorbid substance use disorder in people with schizophrenia, the mortality in the comorbid group has been less studied and with contrasting results. We performed a nationwide open cohort study from 2009 to 2015, including all Norwegians aged 20-79 with schizophrenia and/or substance use disorder registered in any specialized health care setting in Norway, a total of 125,744 individuals. There were 12,318 deaths in the cohort, and total, sex-, age- and cause-specific standardized mortality ratios (SMRs) were calculated, comparing the number of deaths in patients with schizophrenia, schizophrenia only, substance use disorder only or a co-occurring diagnosis of schizophrenia and substance use disorder to the number expected if the patients had the age-, sex- and calendar-year specific death rates of the general population. The SMRs were 4.9 (95% CI 4.7-5.1) for all schizophrenia patients, 4.4 (95% CI 4.2-4.6) in patients with schizophrenia without substance use disorder, 6.6 (95% CI 6.5-6.8) in patients with substance use disorder only, and 7.4 (95% CI 7.0-8.2) in patients with both schizophrenia and substance use disorder. The SMRs were elevated in both genders, in all age groups and for all considered causes of death, and most so in the youngest. Approximately 27% of the excess mortality in all patients with schizophrenia was due to the raised mortality in the subgroup with comorbid SUD. The increased mortality in patients with schizophrenia and/or substance use disorder corresponded to more than 10,000 premature deaths, which constituted 84% of all deaths in the cohort. The persistent mortality gap highlights the importance of securing systematic screening and proper access to somatic health care, and a more effective prevention of premature death from external causes in this group.