Background/Objectives: Few previous studies have evaluated both radiological changes and the clinical effectiveness of platelet-rich plasma (PRP) injections, a biomedical therapy, in patients with chronic discogenic and/or radicular low back pain. Methods: This retrospective comparative cohort study reviewed patients with chronic LBP (>3 months) refractory to first-line conservative therapy between July 2022 and August 2024. Patients who underwent lumbar transforaminal epidural or intradiscal PRP injections, according to clinical presentation and imaging findings, were assigned to the PRP group. (n = 312), while those continuing conservative treatment served as controls (n = 391). Patients receiving both treatments were excluded. Pain and functional outcomes were evaluated using the Numeric Rating Scale (NRS) and Oswestry Disability Index (ODI). Follow-up continued through February 2025. Results: Baseline demographic and clinical characteristics were comparable between groups (p > 0.05). At three months, the PRP group demonstrated significantly greater reductions in pain (NRS: 4.51 ± 0.79 from a baseline of 7.20 ± 0.89) and disability (ODI: 23.73 ± 3.96 from 37.21 ± 3.14), when compared with the conservative group (both p < 0.001). These improvements were sustained at six months (NRS: 2.86 ± 0.80 vs. 6.54 ± 1.99; ODI: 15.37 ± 3.99 vs. 33.70 ± 9.95; both p < 0.001). MRI changes were more frequent in the PRP group (73.09% vs. 9.28%, p < 0.001); however, these findings should be considered exploratory due to potential selection bias in imaging follow-up. Conclusions: PRP injection was associated with greater improvements in pain and function than conservative treatment. MRI improvements were more frequent in the PRP group, but these findings remain exploratory.