PURPOSE: We herein report a case of subacute-onset rhino-orbital mucormycosis (ROM) in an acute leukemia patent caused by the rare but most lethal pathogenic fungus - Cunninghamella. To the best of our knowledge, this is the first case of ROM caused by Cunninghamella reported in China. CASE DESCRIPTION: A 50-year-old Chinese female with acute leukemia (M2 type) who, following the completion of two cycles of chemotherapy, began to exhibit naso-ocular symptoms. The patient was initially diagnosed with extramedullary leukemia. As the disease progressed, the patient began to develop specific black crust-like necrosis of the right eyelids. Following multidisciplinary treatment (MDT) consultation and tissue biopsy, the patient was finally diagnosed with a rare type of ROM caused by Cunninghamella infection. Although the mortality associated with Cunninghamella infection was significantly greater than that associated with infections caused by other Mucorales, the infection was eventually controlled through the adjustment of the antifungal drug regimen and timely surgical intervention. CONCLUSIONS: ROM infection with Cunninghamella is an extremely rare and fatal fungal infection, and early recognition and diagnosis of the disease is critical to the prognosis. The subacute nature of this case may have been a positive factor in the patient's preservation of life.