A 35-year-old female complained of right-sided watery nasal discharge persisting for 2 weeks. Neuroimaging investigations revealed a defect in the lateral side of middle cranial fossa, temporal lobe encephalocele protruding into the lateral extension of the sphenoid sinus, and cerebrospinal fluid (CSF) collection on the right side of the sphenoid sinus. The transcranial approach was performed for resection of the encephalocele and obliteration of the cranial base defect anterolateral to the foramen spinosum with transcranial multilayered closure of the defect using autologous fat, cranial bone graft, and vascularized split temporal muscle. At 1-year follow up, the CSF rhinorrhea had not recurred. Transcranial multilayered closure of the defect is safe and reliable, particularly for large CSF fistula at the far lateral sphenoid sinus.