An extremely rare case of acute necrotizing encephalopathy caused by human herpesvirus-6 variant type B infection is reported. The patient, a 14-month-old previously healthy female, presented with high fever and generalized tonic convulsion followed by rapid deterioration of consciousness. On the second day of the illness, the protein level of the cerebrospinal fluid increased without pleocytosis. On the third day, magnetic resonance images demonstrated symmetric, abnormal signal intensity lesions in the bilateral thalamus, cerebellum, and brainstem. On the fourth day, characteristic maculopapular rash of exanthema subitum appeared on the trunk. Human herpesvirus-6 deoxyribonucleic acid was detected by the polymerase chain reaction in the serum, and immunoglobulin G and immunoglobulin M of serum human herpesvirus-6 were positive. On the twelfth day of illness, the patient died as a result of severe brain damage. Acute necrotizing encephalopathy should be included in the differential diagnosis when examining infants and young children with fulminating consciousness disturbance and intractable convulsion. In addition, as a causative virus, human herpesvirus-6 has to be considered at the pre-eruptive stage of exanthema subitum. Magnetic resonance images are useful because they reveal the characteristic distribution of lesions specific to acute necrotizing encephalopathy.