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Necrotizing fasciitis (NF) is a rapidly progressive and life-threatening soft tissue infection. Although it is known to occur in immunocompromised patients, NF following a single dose of chemotherapy has rarely been reported. We describe a 53-year-old woman with hormone receptor-positive, HER2-negative breast cancer and newly diagnosed type 2 diabetes mellitus who developed NF eight days after receiving her first cycle of dose-dense doxorubicin and cyclophosphamide. Initially mistaken for a drug eruption, her condition deteriorated rapidly despite surgical intervention and intensive care. She died of septic shock, and Group G Streptococcus was identified from blood cultures. This case highlights the need to consider NF in post-chemotherapy patients presenting with erythema and systemic symptoms, even after a single dose, particularly when risk factors such as diabetes and obesity are present. Prompt recognition and intervention remain essential to improve survival.