Objective: To examine whether anti-Black cultural racism moderates the efficacy of psychotherapy interventions among youth. Method: A subset of studies from a previous meta-analysis of 5 decades of youth psychotherapy randomized controlled trials was analyzed. Studies were published in English between 1963 and 2017 and identified through a systematic search. The 194 studies (N = 14,081 participants; age range, 2-19) across 34 states comprised 2,678 effect sizes (ESs) measuring mental health problems (eg, depression) targeted by interventions. Anti-Black cultural racism was operationalized using a composite index of 31 items measuring explicit racial attitudes (obtained from publicly available sources, eg, General Social Survey) aggregated to the state level and linked to the meta-analytic database. Analyses were conducted with samples of majority-Black (ie, >= 50% Black) (n = 36 studies) and majority-White (n = 158 studies) youth. Results: Two-level random-effects meta-regression analyses indicated that higher anti-Black cultural racism was associated with lower ESs for studies with majority-Black youth (beta = -0.2, 95% CI [-0.35, -0.04], p = .02) but was unrelated to ESs for studies with majority-White youth (beta = 0.0004, 95% CI [-0.03, 0.03], p = .98), controlling for relevant area-level covariates. In studies with majority-Black youth, mean ESs were significantly lower in states with the highest anti-Black cultural racism (>1 SD above the mean; Hedges' g = 0.19) compared with states with the lowest racism (<1 SD below the mean; Hedges' g = 0.60). Conclusion: Psychotherapies tested with samples of majority-Black youth were significantly less effective in states with higher (vs lower) levels of antiBlack cultural racism, suggesting that anti-Black cultural racism may be one contextual moderator of treatment effect heterogeneity.