Background: Skull base defects, accidental or planned during tumor resections, present significant reconstructive challenges. Effective repair prevents cerebrospinal fluid (CSF) leaks, meningitis, and pneumocephalus. Methods: This retrospective observational study analyzed 26 patients with anterior or lateral skull base defects treated between 2018 and 2024 at a tertiary care center in Western India. Both planned iatrogenic and accidental intraoperative defects were included. Patient demographics, surgical approach, defect characteristics, reconstruction techniques, and postoperative outcomes were recorded. All patients underwent multilayered repair with tailored perioperative management, including selective lumbar drainage. Results: Among 26 patients, 14 (53.8%) had anterior and 12 (46.2%) had lateral skull base defects. Intraoperative CSF leak occurred in 11 patients (42.3%). Defects were repaired using combinations of autologous tissue (fat, fascia lata, muscle), allogenic grafts (DuraGen), and vascularized flaps. Seven patients (26.9%) required lumbar drains. All reconstructions were successful with no secondary failures. However, two major complications were observed: one case of pneumocephalus and one of postoperative vision loss following ossifying fibroma excision. No postoperative meningitis or recurrent CSF leaks were noted. Conclusion Meticulous multilayered repair strategies and structured perioperative protocols provide excellent outcomes in skull base defect reconstruction. Differentiating between planned and accidental iatrogenic defects allows for better preoperative planning and individualized management. Despite a 100% repair success rate, rare but serious complications such as vision loss highlight the need for careful surgical technique near critical neurovascular structures.