Background: Acremonium strictum (A. strictum) is an opportunistic fungus that is a rare environmental and saprophytic pathogen. Because of its rarity and inadequate mastery of clinicians, A. strictum sphenoid sinusitis becomes a refractory disease in some immunocompetent patients. Moreover, its etiologic and radiological diagnoses are challenging, leading to inappropriate treatment and a protracted course. Case Report: We report a case of A. strictum sphenoid sinusitis in an immunocompetent 74-year-old female patient. She had dizziness and head distension accompanied by intermittent vomiting for 3 months. Computed tomography (CT) suggested a chronic noninvasive fungal sphenoid sinusitis. She underwent a resection of the lesion and postoperative anti-infection therapy. Two months later, the lesions reappeared and were confirmed by CT again. Microbiological culture of purulent tissue revealed a growth of filamentous fungus identified as A. strictum by 26S rRNA sequencing. After 4 weeks of oral voriconazole treatment, the patient recovered and had not relapsed at 2-year follow-up. Conclusions: The rare occurrence of A. strictum as a causative agent of sphenoid sinusitis underscores the importance of utilizing radiological imaging, microbiological culture, and molecular diagnostic techniques to enhance diagnostic accuracy. This case emphasizes the need for heightened clinical suspicion and targeted antifungal therapy to manage fungal infections effectively.