Over the years, the oblique lateral interbody fusion (OLIF) technique has gained significant recognition for treating various spinal conditions in lumbar segments L2-L5. However, the adoption of OLIF for the L5-S1 segment has not been widely embraced by the spinal surgery community, given that significant concerns remain regarding the applicability of OLIF for lumbosacral fusion. In this study, a cohort of 20 patients underwent interbody fusion at the L5-S1 level using the OLIF technique through a single retroperitoneal oblique approach positioned between the Psoas muscle and the great vessels. The procedure involved discectomy and endplate preparation accomplished through a surgical window created on the anterolateral side of the L5-S1 disc. For secure interbody fusion cage placement, a supplementary cage insertion approach was employed. All patients were followed up for a minimum of 12 months. The mean preoperative visual analog scale (VAS) score for lower back pain was 6.3 ± 1.5 and experienced a significant reduction to 1.2 ± 0.8 at 12 months. The VAS score for lower limb pain significantly decreased from 5.6 ± 1.4 preoperatively to 0.8 ± 0.3 at 12 months after the surgery. Furthermore, the preoperative Oswestry disability index (ODI) improved from 82.4% ± 16.2% to 8.1% ± 2.0% at 12 months. Radiographic evaluations after surgery confirmed improved lumbosacral junction reconstruction for all patients. At the final follow-up, successful bony fusion was observed in all cases. Based on these findings, the OLIF technique for L5-S1 fusion represents an attainable approach for lumbosacral reconstruction. The procedure's success hinges on a comprehensive preoperative plan and precise intraoperative techniques.