This referral center prospective inception cohort study included 84 consecutive children having extracorporeal membrane oxygenation (ECMO) for noncardiac illness indications at the age of less than 6 years from 2000 to 2017. Long-term outcomes were survival, neurocognitive (Wechsler Preschool and Primary Scales of Intelligence) and functional (General Adaptive Composite) scores, and disability, with optimal outcome defined as scores greater than or equal to 80 and without disability. Age at cannulation was 551 (standard deviation [SD] = 571) days, 40 (47.6%) were male, 12 (14.3%) had known chromosomal abnormality, and 15 (17.9%) had nonchromosomal congenital abnormality. Survival was 45 (53.6%) to hospital discharge, and 41 (48.8%) to age 6 years. In 40/41 (97.6%) survivors with follow-up, at mean age of 56.1 (SD = 5.1) months, neurocognitive and functional scores were shifted to the left, with 30–42.5% having a score greater than 2 SD below population norms. Optimal outcome occurred in 11/40 (27.5%) survivors, and 11/84 (13.1%) overall. On multiple regression full-scale intelligence quotient was associated with longer time in pediatric intensive care unit (PICU) pre-ECMO (OR per hour −0.02, 95% confidence interval [CI] = −0.03 to −0.01; p = 0.005), known chromosomal abnormality (odds ratio [OR] = −18.99, 95% CI = −29.04 to −8.04; p = 0.001), and seizure pre-ECMO (OR = −17.00, 95% CI = −30.00 to −4.00; p = 0.012). Predictors of mortality included peak lactate on ECMO and nonchromosomal congenital abnormality. Findings may help with ECMO decision-making and counseling.