The vaccines manufactured by Pfizer, Moderna, and AstraZeneca to prevent the spread of SARS-CoV-2 have been reported to cause a wide range of adverse cutaneous reactions. The most common of these include delayed large local reactions, injection site reactions, urticaria, and morbilliform eruptions. The rarest and severe cutaneous reactions include the development of autoimmune blistering diseases such as pemphigus vulgaris and bullous pemphigoid. In this case report, we present a 73-year-old female patient who developed de novo pemphigus vulgaris two weeks after receiving the Pfizer-BioNTech COVID-19 vaccine. To the best of our knowledge, ours is the first case of new-onset pemphigus vulgaris following the Pfizer COVID-19 vaccine in the United States and only the third worldwide. This report confirms a suspected association between COVID-19 vaccination and the onset of pemphigus vulgaris, although it is exceedingly rare. It also highlights the importance of considering the COVID-19 mRNA vaccines as etiologies for new-onset pemphigus vulgaris and potentially other autoimmune blistering disorders. This knowledge may be important for medical providers when considering a differential diagnosis of new-onset blistering disease to expedite accurate diagnosis and initiation of treatment.