Chimeric antigen receptor (CAR) T-cell therapy leads to durable remissions in relapsed B-cell cancers, but treatment-associated immunocompromise leads to a substantial morbidity and mortality risk from atypical infection. Mucormycosis is an aggressive and invasive fungal infection with a mortality risk of 40–80% in patients with haematological malignancies. In this Grand Round, we report a case of mucormycosis in a 54-year-old patient undergoing CAR T-cell therapy who reached complete clinical control of Mucorales with combined aggressive surgical debridement, antifungal pharmacotherapy, and reversal of underlying risk factors, but with substantial morbidity from extensive oro-facial surgery affecting the patient’s speech and swallowing. For broader context, we present our case alongside an US Food and Drugs Administration adverse events reporting database analysis and a review of the literature to fully evaluate the clinical burden of mucormycosis in patients treated with CAR T-cell therapy. We discuss epidemiology, clinical features, diagnostic tools, and current frameworks for treatment and prophylaxis. We did this analysis to promote increased vigilance for mucormycosis among physicians specialising in CAR T-cell therapy and microbiologists and to illustrate the importance of early initiation of therapy to effectively manage this condition. Mucormycosis prevention and early diagnosis, through targeted surveillance and mould prevention in patients at highest risk and Mucorales-specific screening assays, is likely to be key to improving outcomes in patients treated with CAR T-cell therapy.