Background Benzodiazepine-positive overdoses increased between 2019 and 2021 in Tennessee. We sought to determine the changes in the number and characteristics of prescription and illicit benzodiazepine-positive fatal drug overdoses during this period. Materials and Methods A statewide study was conducted to determine changes in the number and characteristics of benzodiazepine-positive drug overdose decedents using 2019–2021 data from the Tennessee State Unintentional Drug Overdose Reporting System. The analyses were limited to Tennessee residents aged ≥ 18 years. A benzodiazepine-positive overdose was defined as any benzodiazepine on toxicology, regardless of the presence of other substances. Frequencies were generated to compare demographics, circumstances, prescription history, and toxicology between 2019 and 2021 for illicit and prescription benzodiazepine-positive fatal overdoses. Results Between 2019 and 2021, 1666 benzodiazepine-positive unintentional or undetermined fatal drug overdoses out of 5916 total overdoses that occurred among adult Tennessee residents with available toxicological information. Prescription benzodiazepines were identified in 80.7% of deaths, whereas illicit benzodiazepines were identified in 12.0% of deaths. Many decedents had an anxiety disorder (45.5%), while over half of all decedents had a history of substance use disorder (52.3%). Most benzodiazepine-positive overdoses involved fentanyl (71.3%). Conclusions This analysis can inform local and regional public health workers to implement focused prevention and intervention efforts for people with co-occurring mental health conditions and substance use disorders to curb overdose epidemics among persons using benzodiazepines in Tennessee. Public health campaigns should focus on educating people on appropriate prescription medication use and the dangers of obtaining substances illicitly. Given the high proportion of opioids in this population, further education also is needed on the dangers of polysubstance drug use. The differences between prescription and illicit benzodiazepine-positive fatal overdoses indicate the need to develop substance-specific prevention and treatment strategies.