Women carry a substantial burden of psychiatric, somatic and lifestyle-related morbidity in the prison context. By describing causes of death and estimating the risk and burden of mortality compared with the general population, this study investigates how mortality operates in this highly marginalized and under-researched population. In this registry-based study of all women incarcerated in Norwegian prisons from 2000 to 2019 (N = 11 313), we calculated crude mortality rates, years of lost life and, by using mortality in age-matched women from the general population as a reference, age-standardized mortality ratios and years of lost life rates. Over a mean follow-up time of 10.7 years, at a median age of 50years, 9% of the population had died (n = 1005). Most deaths (80%) were premature deaths from an avoidable cause. Drug-induced causes and deaths from major non-communicable diseases (NCDs) were most frequent (both 32%). Compared with women in the general population, women with a history of incarceration were more likely to die from any cause. Trends in annual age-standardized years of lost life rates suggest that the mortality burden associated with major NCDs has gradually replaced drug-induced causes. Women with a history of incarceration die at a greater rate than their peers and largely from avoidable causes. The profile of causes contributing to the substantial burden of mortality placed on this population has changed over time and has important implications for future efforts to reduce morbidity and the risk of premature death following release from prison.