Cutaneous adverse reactions to mRNA COVID-19 vaccines in patients with preexisting dermatologic disease include bullous eruptions, pityriasis rubra pilaris, dermatomyositis, and granuloma annulare. Erythroderma is a rare but severe adverse reaction not previously seen. This case report describes the development of erythroderma in a 73-year-old male with a history of atopic dermatitis, with widespread erythema and scaling covering 95% of his body surface area, which developed sequentially after receiving each dose of the Pfizer-BioNTech (BNT162b2) COVID-19 vaccination. The patient's condition improved significantly with appropriate dermatologic treatment, including systemic and topical corticosteroids and dupilumab. Thus, it is imperative to recognize erythroderma as a potential side effect of the Pfizer-BioNTech COVID-19 vaccine, particularly in patients with preexisting dermatologic conditions. Early diagnosis and treatment are vital for managing this potentially life-threatening reaction and preventing severe complications.