Administering myelosuppressive chemotherapy to patients with aggressive malignant hematologic disorders typically poses serious infectious complications, which can be exacerbated by the presence of active COVID-19 infection. We report on a case of a successfully treated fit elderly woman with refractory acute myeloid leukemia (AML) who also had mild COVID-19 infection and detectable viral load at the time she was found to have recurrent disease. Prior to initiation of reinduction treatment with cytarabine/idarubicin, this 2-dose COVID-19-vaccinated patient received antiviral therapy with remdesivir with resolution of upper respiratory symptoms. This was followed by sotrovimab on the third day of chemotherapy. Throughout her hospital course, she remained hemodynamically stable with one episode of neutropenic fever without other identified infections. Symptomatic reactivation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 was not observed. After achieving biopsy-confirmed morphologic remission of AML and with neutrophil recovery, the patient gradually cleared the virus, eventually testing negative on polymerase chain reaction test of the nasopharynx. This case underlines the importance of considering initiation of timely chemotherapy, although myelosuppressive, in appropriate patients with aggressive hematologic malignancies and concomitant SARS-CoV-2. It demonstrates management of active COVID-19 infection in this group of patients and the dynamics of SARS-CoV-2 viral load during leukemia treatment.