U.S. prisons were especially susceptible to COVID-19 infection and death; however, data limitations have precluded a national accounting of prison mortality (including but not limited to COVID-19 mortality) during the pandemic. Our analysis of mortality data collected from public records requests (supplemented with publicly available data) from 48 Departments of Corrections provides the most comprehensive understanding to date of in-custody mortality during 2020. We find that total mortality increased by 77% in 2020 relative to 2019, corresponding to 3.4 times the mortality increase in the general population, and that mortality in prisons increased across all age groups (49 and under, 50 to 64, and 65 and older). COVID-19 was the primary driver for increases in mortality due to natural causes; some states also experienced substantial increases due to unnatural causes. These findings provide critical information about the pandemic's toll on some of the country's most vulnerable individuals while underscoring the need for data transparency and standardized reporting in carceral settings.