Background: Adult degenerative lumbar spondylolisthesis (ADLS) commonly causes chronic low back pain and radiculopathy. Transforaminal Lumbar Interbody Fusion (TLIF) enables decompression, reduction, and fusion through a single posterior approach with potential biomechanical advantages. This study evaluated surgical and functional outcomes following TLIF in ADLS patients. Materials and Methods: A prospective observational study was conducted in the Department of Neurosurgery, MKCG Medical College and Hospital, Berhampur (December 2019–December 2021). Fifty adults (45–60 years) with degenerative lumbar spondylolisthesis (Grade III–IV or Grade I–II unresponsive to conservative therapy) underwent TLIF. Pain, disability, and quality of life were assessed preoperatively and at 10 days, 1 month, and 6 months postoperatively using the Visual Analogue Scale (VAS), Oswestry Disability Index (ODI), and Short Form-36 (SF-36). Data were analyzed using SPSS 25; p < 0.05 was considered significant. Results: The mean age was 51.36 ± 4.5 years; 60% were male. Mean operative time was 3.5 hours with average blood loss of 230 ml. Complete correction of slip was achieved in all Grade I–II cases and partial correction in higher grades. No screw breakage, infection, neurological deficit, or slip progression occurred. SF-36 scores improved from 1536.4 preoperatively to 2576.3 at 6 months (p < 0.001). VAS and ODI scores also showed significant and sustained improvement. Discussion and Conclusion: TLIF proved to be a safe, effective, and biomechanically superior technique for managing degenerative and high-grade spondylolisthesis. It provided stable fusion, significant pain relief, improved function, and enhanced quality of life with minimal complications. Further long-term studies are warranted to confirm durability of outcomes.