Introduction The heightened risk of coronavirus disease 2019 (COVID-19) infection and mortality in prisons is well documented, but COVID-19’s impact on all-cause mortality in incarcerated populations has not yet been studied. This study analyzed mortality records from the Florida State Department of Corrections (FLDOC) prison system population to evaluate the impact COVID-19 had on all-cause mortality and compare mortality rates and life expectancy in FLDOC with that of the overall state of Florida population. Methods Population age and sex data for FLDOC were ascertained from the FLDOC Offender Based Information System. FLDOC death data by age, sex, and cause of death were acquired from medical records and FLDOC offender reports. The state of Florida demographic and death data were collected from the Census Bureau, Florida Department of Health, and Centers for Disease Control and Prevention. All data were collected for the years 2019 and 2020. Age- and sex-standardized life table measures were calculated and COVID-19 contribution to changes in life expectancy were assessed using Arriaga's decomposition. Results The standardized mortality rate in the FLDOC population increased by 45% between 2019 and 2020, causing an overall 4.0-year decline in life expectancy. Over the same period, the state of Florida population's standardized mortality increased by 19%, resulting in an overall 2.7-year decline in life expectancy. Within the FLDOC population, life expectancy decline could be attributed exclusively to COVID-19 mortality. Conclusions The state of Florida prison population saw a substantial increase in mortality driven solely by COVID-19 mortality, leading to an overall 4-year decline in life expectancy. Given the findings and continued threat of COVID-19 outbreaks, FLDOC and other prison systems should strive to increase vaccination uptake, decrease prison populations, and commit to COVID-19 data transparency.