Cerebrospinal fluid (CSF) leak and encephalocele from the middle cranial fossa into the sphenoid sinus lateral recess (SSLR) is a rare condition. It is often associated with obesity, female sex, well-pneumatized sinus, and prolonged intracranial hypertension. Endoscopic repair has emerged as the mainstay treatment with a success rate increasing to over 90% by refining reconstruction methods and controlling intracranial pressure. Here, we describe how a female with SSLR CSF leak and encephalocele successfully managed with endoscopic transpterygoid approach and multilayered repair. The defect was closed using four indifferent tissues, including the duragen patch, sinus mucosal flaps, the middle turbinate bone, and free mucosa flap, from the inside out. The patient had an uneventful postsurgical course and remained disease-free during the 9-month follow-up. To conclude, the technique of using sinus mucosal flaps in the context of multilayered reconstruction might be a useful method to repair CSF leak.