IMPORTANCE: Anxiety and depression affect 30% of youth but are markedly undertreated compared with other mental disorders, especially in Hispanic populations. OBJECTIVE: To examine whether a pediatrics-based behavioral intervention targeting anxiety and depression improves clinical outcome compared with referral to outpatient community mental health care. DESIGN, SETTING, AND PARTICIPANTS: This 2-center randomized clinical trial with masked outcome assessment conducted between brief behavioral therapy (BBT) and assisted referral to care (ARC) studied 185 youths (aged 8.0-16.9 years) from 9 pediatric clinics in San Diego, California, and Pittsburgh, Pennsylvania, recruited from October 6, 2010, through December 5, 2014. Youths who met DSM-IV criteria for full or probable diagnoses of separation anxiety disorder, generalized anxiety disorder, social phobia, major depression, dysthymic disorder, and/or minor depression; lived with a consenting legal guardian for at least 6 months; and spoke English were included in the study. Exclusions included receipt of alternate treatment for anxiety or depression, presence of a suicidal plan, bipolar disorder, psychosis, posttraumatic stress disorder, substance dependence, current abuse, intellectual disability, or unstable serious physical illness. INTERVENTIONS: The BBT consisted of 8 to 12 weekly 45-minute sessions of behavioral therapy delivered in pediatric clinics by master’s-level clinicians. The ARC families received personalized referrals to mental health care and check-in calls to support accessing care from master’s-level coordinators. MAIN OUTCOMES AND MEASURES: The primary outcome was clinically significant improvement on the Clinical Global Impression–Improvement scale (score ≤2). Secondary outcomes included the Pediatric Anxiety Rating Scale, Children's Depression Rating Scale–Revised, and functioning. RESULTS: A total of 185 patients were enrolled in the study (mean SD age, 11.3 2.6 years; 107 57.8% female; 144 77.8% white; and 38 20.7% Hispanic). Youths in the BBT group (n = 95), compared with those in the ARC group (n = 90), had significantly higher rates of clinical improvement (56.8% vs 28.2%; χ21 = 13.09, P < .001; number needed to treat, 4), greater reductions in symptoms (F2,146 = 5.72; P = .004; Cohen f = 0.28), and better functioning (mean SD, 68.5 10.7 vs 61.9 11.9; t156 = 3.64; P < .001; Cohen d = 0.58). Ethnicity moderated outcomes, with Hispanic youth having substantially stronger response to BBT (76.5%) than ARC (7.1%) (χ21 = 14.90; P < .001; number needed to treat, 2). Effects were robust across sites. CONCLUSIONS AND RELEVANCE: A pediatric-based brief behavioral intervention for anxiety and depression is associated with benefits superior to those of assisted referral to outpatient mental health care. Effects were especially strong for Hispanic participants, suggesting that the protocol may be a useful tool in addressing ethnic disparities in care. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01147614.