Cerebral vasculitis is a long-standing but flourishing and fadeless research topic. Infections are a frequent cause of cerebral vasculitis, vital to diagnose due to involvement of specific anti-infection treatments. A 65-year-old man visited the hospital for his neurological symptoms without obvious inducements. After admission, radiological examination and comprehensive conventional microbiological tests (CMTs) revealed suspected intracranial infectious vasculitis. Metagenomic next-generation sequencing (mNGS) and reverse transcription-polymerase chain reaction further confirmed that his cerebral vasculitis was caused by Talaromyces marneffei (T. marneffei) and Aspergillus niger (A. niger) co-infection. The patient’s final diagnosis changed from initial herpetic encephalitis, due to the past history of cephalosome and facial herpes and non-significant antiviral therapeutic effects, to fungal cerebral vasculitis. The patient was discharged after use of targeted antifungal therapies on day 18 of his admission, and his associated symptoms disappeared completely at follow-up 3 weeks later. We first illustrated the presence of uncommon cerebral vasculitis caused by T. marneffei and A. niger in a human immunodeficiency virus-positive patient. In clinically suspected patients with infectious cerebral vasculitis, mNGS should be performed to detect potential pathogens if CMTs may not provide useful pathogenic clues, highlighting the importance of mNGS in the diagnosis and treatment of infectious diseases.