The first-line treatment for nonspecific low back pain (LBP) relief is physical exercise; however, there is no uniformity in recommendations regarding the type of exercise, and physicians predominantly prescribe pharmacological treatments. This creates a treatment gap in non-pharmacological management of LBP. Preliminary data suggest that manual therapy and acupressure could be relevant therapeutic options. The primary objective of this study was to describe the evolution of pain in patients with nonspecific LBP persisting for at least 4 weeks who received 2 treatment sessions combining manual therapy with acupressure (Biokinergie® method) as part of their routine management. In this prospective, observational, and non-interventional study, participants were monitored on the days of manual therapy session delivery (initial visit on Day 0 and follow-up visit on Day 21). Follow-up assessments occurred 3 days and 3 weeks post-therapy sessions. A total of 114 participants suffering from LBP for a median duration of 11.9 weeks were enrolled from May 2021 to May 2023. The intensity of average pain experienced over a 24-hour period was significantly reduced on Day 24 (−36.0 ± 27.2 mm on a visual analog scale of 100 mm, P < .001), with 82 (75.2%) participants reporting a decrease of at least 20 mm. Participants reported significant reductions in pain (−25.9 ± 23.9 mm on Day 3, −29.7 ± 26.7 mm on Day 21, and −40.9 ± 28.3 mm on Day 42, P < .001) and functional disability (Roland-Morris Disability Questionnaire score: −5.4 ± 0.4 points on Day 21 and −7.4 ± 0.4 points on Day 42, P < .001). This was associated with an improved Dallas Pain Questionnaire score, indicating a reduced impact of LBP on daily activities (−27.2 ± 2.0% on Day 21 and −35.8 ± 2.0% on Day 42, P < .001). Posttreatment, most participants (86.3%) reported reduced analgesic intake compared to baseline, and 83.3% were very satisfied with the therapy. A significant and clinically relevant reduction in lumbar pain was observed after 2 sessions of manual therapy combined with acupressure, paving the way for future clinical research.