Background. Heartland virus (HRTV) is a tick-borne phlebovirus recently described in Missouri that is associated with fever, leukopenia, and thrombocytopenia. The virus has also been detected in Ambylomma americanum ticks. Methods. Here we report the first fatal case of HRTV disease in an 80-year-old Tennessee resident. He was hospitalized with fever, confusion, leukopenia, and thrombocytopenia and developed multiorgan failure and hemorrhage. A tick-borne illness was suspected and testing for ehrlichiosis was negative. He died on hospital day 15, and autopsy specimens were tested for various pathogens as part of an unexplained death evaluation. Results. HRTV antigens were detected in postmortem spleen and lymph nodes by immunohistochemistry, and HRTV was detected in premortem blood by reverse transcription polymerase chain reaction and by isolation in cell culture. Conclusions. This case demonstrates that HRTV infection can cause severe disease and death and expands the geographic range of HRTV within the United States.