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Low back pain (LBP) is common in adolescence, but there is a paucity of high-quality research to inform care. We conducted a multicenter randomized trial comparing 12 weeks of spinal manipulative therapy (SMT) combined with exercise therapy (ET) to ET alone. Participants were 185 adolescents aged 12 to 18 years with chronic LBP. The primary outcome was LBP severity at 12, 26, and 52 weeks. Secondary outcomes included disability, quality of life, medication use, patient- and caregiver-rated improvement, and satisfaction. Outcomes were analyzed using longitudinal linear mixed effect models. An omnibus test assessing differences in individual outcomes over the entire year controlled for multiplicity. Of the 185 enrolled patients, 179 (97%) provided data at 12 weeks and 174 (94%) at 26 and 52 weeks. Adding SMT to ET resulted in a larger reduction in LBP severity over the course of 1 year (P = 0.007). The group difference in LBP severity (0-10 scale) was small at the end of treatment (mean difference = 0.5; P = 0.08) but was larger at weeks 26 (mean difference = 1.1; P = 0.001) and 52 (mean difference = 0.8; P = 0.009). At 26 weeks, SMT with ET performed better than ET alone for disability (P = 0.04) and improvement (P = 0.02). The SMT with ET group reported significantly greater satisfaction with care at all time points (P ≤ 0.02). There were no serious treatment-related adverse events. For adolescents with chronic LBP, spinal manipulation combined with exercise was more effective than exercise alone over a 1-year period, with the largest differences occurring at 6 months. These findings warrant replication and evaluation of cost effectiveness.