Early intervention for adolescent substance use and mental health problems may mitigate potential harm. We examined patient outcomes from a pragmatic trial of two modalities of delivering screening, brief intervention, and referral to treatment (SBIRT) and usual care (UC) in pediatric primary care. All clinic pediatricians (n = 52) were randomized to three arms: (1) pediatrician-only, in which pediatricians were trained to deliver SBIRT; (2) embedded behavioral clinician (BC), in which pediatricians were trained to refer eligible adolescents to a BC who administered SBIRT; and (3) UC. Using electronic health record data, changes in past year substance use and depression symptoms between the index visit and next screening visit were examined across treatment arms. Among patients who endorsed substance use and/or depression symptoms or were eligible for further assessments, brief interventions, and referrals based on clinician assessment at the index visit, 648 patients (mean age = 15.2 [standard deviation = 1.2]) were rescreened at a follow-up visit between 6 months and 2 years later. Among all patients, self-reported substance use rates did not differ over time or across arms, and depression symptoms increased over time. The embedded BC arm had lower odds of having depression symptoms at follow-up than the physician-only arm, and lower odds than the UC arm although not significant; we found no differences between the pediatrician-only and UC arms. The increase in depression symptoms over time highlights this population’s vulnerability and the importance of developing appropriate interventions. An embedded BC in pediatric primary care trained in SBIRT may benefit patients with depression symptoms.