IMPORTANCE: Cognitive behavioral therapy (CBT) skills training interventions are recommended first-line nonpharmacologic treatment for chronic pain, yet they are not widely accessible. OBJECTIVE: To examine effectiveness of remote, scalable CBT-based chronic pain (CBT-CP) treatments (telehealth and self-completed online) for individuals with high-impact chronic pain, compared with usual care. DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness, 3-group, phase 3 randomized clinical trial enrolled 2331 eligible patients with high-impact chronic musculoskeletal pain from 4 geographically diverse health care systems in the US from January 2021 through February 2023. Follow-up concluded in April 2024. INTERVENTIONS: Participants were randomized 1:1:1 to 1 of 2 remote, 8-session, CBT-based skills training treatments: health coach-led via telephone/videoconferencing (health coach; n = 778) or online self-completed program (painTRAINER; n = 776); or to usual care plus a resource guide (n = 777). MAIN OUTCOMES AND MEASURES: The primary outcome was attaining or exceeding the minimal clinically important difference (MCID) in pain severity score (≥30% decrease; score range, 0-10) on the 11-item Brief Pain Inventory-Short Form from baseline to 3 months; 6 and 12 months from baseline were secondary time points. Secondary outcomes at 3, 6, and 12 months included pain intensity, pain-related interference, PROMIS (Patient-Reported Outcomes Measurement Information System) social role and physical functioning; and patient global impression of change. RESULTS: Among 2331 eligible randomized individuals (mean age, 58.8 [SD, 14.3] years; 1712 [74%] women; 1030 [44%] rural/medically underserved), 2210 (94.8%) completed the trial. At 3 months, the adjusted percentage of participants achieving 30% or greater decrease in pain severity score was 32.0 (95% CI, 29.3-35.0) in the health coach group, 26.6 (95% CI, 23.4-30.2) in the painTRAINER group, and 20.8 (95% CI, 18.0-24.0) in the usual care group. Both intervention groups were significantly more likely to attain an MCID in pain severity compared with control (health coach vs usual care: relative risk [RR], 1.54 [95% CI, 1.30-1.82]; painTRAINER vs usual care: RR, 1.28 [95% CI, 1.06-1.55]), and the health coach program was more effective than the online self-completed painTRAINER program (health coach vs painTRAINER: RR, 1.20 [95% CI, 1.03-1.40]). Statistically significant benefits were observed for both intervention groups vs usual care at 6 and 12 months after randomization for the pain severity outcomes and for other secondary pain and functioning outcomes. CONCLUSIONS AND RELEVANCE: Remote, scalable CBT-CP treatments (delivered either via telehealth or self-completed modules online) resulted in modest improvements in pain and related functional/quality-of-life outcomes compared with usual care among individuals with high-impact chronic pain. These lower-resource CBT-CP treatments could improve availability of evidence-based nonpharmacologic pain treatments within health care systems. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04523714.