Low back pain (LBP) is one of the most common and costly musculoskeletal conditions impacting health care in the United States. The development of multimodal strategies of treatment is imperative in order to curb the growing incidence and prevalence of LBP. Spinal manipulative therapy (SMT), dry needling (DN), and exercise are common nonpharmacological treatments for LBP. This study is a 3-armed parallel-group design randomized clinical trial. We enrolled and randomized 96 participants with LBP into a multimodal strategy of treatment consisting of a combination of DN and SMT, DN only, and SMT only, followed by an at-home exercise program. All participants received 4 treatment sessions in the first 2 weeks followed by a 2-week home exercise program. Outcomes included clinical (Oswestry Disability Index, numeric pain intensity rating) and mechanistic (lumbar multifidus, erector spinae, and gluteus medius muscle activation) measures at baseline, 2, and 4 weeks. Participants in the DN and SMT groups showed larger effects and statistically significant improvement in pain and disability scores, and muscle percent thickness change at 2 weeks and 4 weeks of treatment when compared to the other groups. This study was registered prior to participant enrollment. PERSPECTIVE: This article presents the process of developing an optimized multimodal treatment plan utilizing SMT, DN, and exercise to address the burden of LBP for impacted individuals and the health care system. This method could potentially help clinicians who treat LBP to lower initial pain and increase exercise compliance. (clinicaltrials.gov NCT05802901). Keywords: Low back pain; dry needling; exercise; spinal manipulative therapy.