Chronic pain after traumatic brain injury (TBI) is prevalent and associated with poor outcomes. By providing multidisciplinary care through expert consultation, a collaborative care (CC) treatment approach may reduce pain interference. To compare CC with usual care (UC) in decreasing pain interference. This randomized clinical trial was conducted from July 2018 through April 2021 at 2 hospital-based academic rehabilitation medicine clinics in Seattle, Washington. Participants included adults with mild-to-severe TBI (at least 6 months before enrollment) and chronic pain. Data analysis was performed from March 30, 2022, to August 30, 2023. The CC intervention (called TBI Care) included up to 12 in-person or telephone visits over 16 weeks with a care manager (CM) who provided person-centered cognitive behavioral treatment. The CM met weekly with members of the expert team to review participants and discuss recommendations to optimize treatment. The primary outcome was pain interference on the Brief Pain Inventory at treatment conclusion (4 months after randomization). Secondary outcomes included pain interference at 8 months; pain severity; symptoms of depression, anxiety, and sleep disturbance; pain-related emergency department visits; community participation; and participant satisfaction. Linear mixed-effects regression was used for analysis. A total of 1379 individuals were screened for eligibility, and 158 were randomized (79 to CC and 79 to UC). The participants were mostly women (92 participants [58%]) with a mean (SD) age of 46.8 (13.2) years and a mean (SD) of 15.3 (3.0) years of education. TBI occurred a mean (SD) of 4.0 (5.9) years (median [IQR], 1.9 [0.8-4.5] years) before enrollment. All TBI severities were included, and of 149 participants for whom TBI severity was known, the majority (97 participants [65%]) had mild TBI. In the CC group, 71 participants (90%) completed at least 11 sessions, and, at 4 months, this group had significantly lower pain interference scores compared with the UC group (mean [SD], 3.46 [2.17] vs 5.03 [2.28]). This difference was maintained at 8 months after randomization, with mean (SD) TBI care pain interference scores of 3.61 (2.22) for CC vs 4.68 (2.51) for UC. At 4 months, there was significantly lower pain severity in the CC group vs UC group (mean [SD] score, 3.63 [1.95] vs 4.90 [1.96]), as well as symptoms of depression (mean [SD] score, 8.07 [5.34] vs 11.31 [6.37]) and anxiety (mean [SD], 6.20 [5.17] vs 9.58 [6.00]). Satisfaction with pain treatment (mean [SD] score, 2.99 [1.23] vs 2.52 [1.25]), clinical care (mean [SD] score, 3.28 [1.00] vs 2.84 [1.26]), and overall health care (mean [SD] score, 3.25 [0.88] vs 2.82 [1.00]) were significantly higher in the CC group vs the UC group; global impression of change was significantly lower in the CC group vs the UC group (mean [SD] score, 2.74 [1.02] vs 3.47 [1.26]) (lower scores denote a better impression of change). In this randomized clinical trial of CC compared with UC for patients with TBI, CC was effective at reducing pain interference and was sustained at 8-month follow-up. Further research is needed to examine the implementation and cost-effectiveness of CC for TBI in other health care settings. ClinicalTrials.gov Identifier: NCT03523923.