BACKGROUND: Despite advances in treatment, survival from acute lymphoblastic leukemia (ALL) remains lower among non-White children than White children in the US. We investigated the association of race/ethnicity and socioeconomic status (SES) with survival. PROCEDURES: We analyzed 9,295 Californian children (3,251 Whites, 4,890 Hispanics, 796 Asians, and 358 Blacks) aged ≤ 19 years diagnosed with a first primary ALL during 1988-2011. We used the Kaplan-Meier method to estimate survival at 1, 5, and 10 years after diagnosis for three calendar periods. Hazard ratios of death for race/ethnicity, SES, and clinical factors were estimated by Cox regression models. RESULTS: Median follow-up time was 7.4 years (range 0-25 years). Over time, survival after ALL improved steadily, but inequalities persisted across races/ethnicities. Five-year survival (95% confidence interval) was 85.0% (83.6-86.2) for White, 81.4% (78.3-84.0) for Asian, 79.0% (77.8-80.2) for Hispanic, and 74.4% (69.4-78.8) for Black children. In multivariable-adjusted models, the hazard of death was increased by 57% among Black, 38% among Hispanic, and 33% among Asian children compared with White children. Patients residing in the lowest SES neighborhoods at diagnosis had a 39% increased risk of death relative to those living in higher SES neighborhoods. CONCLUSION: Despite significant improvements in survival, non-White children and children residing in low SES neighborhoods experienced worse survival even after adjusting for potential confounders. Our findings highlight the need to capture specific information on disease biology, treatment, and treatment adherence to better understand the predictors of lower survival in minority and low SES groups.