Background Acute low back pain is a leading cause of disability worldwide. While clinical guidelines offer general management strategies, real-world evidence on nerve block therapy for acute low back pain in primary care remains limited. Methods We conducted a prospective, multicenter observational cohort study at 19 private pain clinics in Japan from June 2021 to March 2022. Patients with acute low back pain onset within the past seven days were enrolled and followed for seven days. Clinical decisions, including nerve block administration, were made at the physician's discretion. Patient-reported outcomes were collected via web- or paper-based questionnaires and compared between patients who received nerve block injections and those who did not. The primary outcome was the change in Pain Disability Assessment Scale (PDAS) scores from baseline to Day 3; secondary outcomes included PDAS changes on Day 7 and Visual Analog Scale (VAS) scores for seven consecutive days. Multivariable regression models were used to adjust for confounding factors. Results A total of 567 patients were analyzed (523 injected; 44 non-injected). Among patients with baseline PDAS scores ≥ 45, those who received injections showed significantly greater improvement on Day 3. The mean differences (95％ confidence interval (CI) ) in PDAS scores were -6.42 (-12.48 to -0.36) ( = 0.038) at a baseline score of 45, -11.95 (-21.35 to -2.55) ( = 0.013) at 50, and -17.54 (-31.01 to -4.07) ( = 0.011) at 55. VAS scores were significantly lower in patients with the injection on Day 1 (mean difference (95% CI): -0.70 (-1.37 to -0.04)) and Day 3 (-0.76 (-1.44 to -0.08)), with no significant differences beyond Day 3. Conclusion Nerve block therapy was associated with faster pain relief and earlier functional improvement in acute low back pain patients, particularly among those with greater baseline disability. These findings provide meaningful real-world evidence. Given the observational design and the fact that treatment decisions were made at the discretion of attending physicians, there remains a potential for selection bias. Further well-designed studies are needed to validate these findings and guide optimal treatment strategies for acute low back pain.