**Objective:** We examined whether anti-Black cultural racism moderates the efficacy of psychotherapy interventions among youth. **Method:** We analyzed a subset of studies from a previous meta-analysis of five decades of youth psychotherapy randomized controlled trials. Studies were published in English between 1963 and 2017 and identified through a systematic search. The 194 studies (N=14,081; ages 2-19) across 34 states comprised 2,678 effect sizes (ESs) measuring mental health problems (e.g., 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; e.g., General Social Survey), aggregated to the state level and linked to the meta-analytic database. Analyses were conducted with samples of majority (i.e., ≥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 (β=-0.20, CI: -0.35, -0.04, p=0.02) but was unrelated to ESs for studies with majority-White youth (β=0.0004, CI: -0.03, 0.03, p=0.98), 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; g=0.19) compared to states with the lowest racism (<1 SD below the mean; g=0.60). **Conclusions:** Psychotherapy randomized controlled trials with samples comprised of majority-Black youth were significantly less effective in states with higher (vs. lower) levels of anti-Black cultural racism, suggesting that anti-Black cultural racism may be one contextual moderator of treatment effect heterogeneity.