This referral center’s prospective inception-cohort study from 1989 to 2000 (Era 1) and 2000 to 2022 (Era 2) included 232 consecutive children having neonatal respiratory extracorporeal membrane oxygenation (ECMO). Kindergarten-age outcomes determined in 137/139 (95.8%) survivors were Wechsler Preschool and Primary Scales of Intelligence, Beery–Buktenica Developmental Test of Visual-Motor Integration (VMI), and sensorimotor disability, with optimal outcome defined as scores greater than or equal to 80 and without disability. In Era 2, there were fewer patients/year, fewer neonates with meconium aspiration syndrome, and more with sepsis, lethal disease, or “other” diagnoses. Era 2 also had higher rates of venoarterial cannulation, cannulation after the first week of life, and extracorporeal cardiopulmonary resuscitation. In survivors, there was a shift in Full-Scale Intelligence Quotient (FSIQ), Verbal IQ, Performance IQ, and VMI to the left of population norms, with scores less than 70 in 16–40% (expected in 2.27% of the normative population), disability in 53%, and optimal outcome in 38%. Era was not independently associated with mortality, optimal outcome, or FSIQ outcomes. Congenital Diaphragmatic Hernia (CDH) was independently associated with lower optimal outcome and FSIQ. Sensorineural hearing loss (bilateral, predominantly high-frequency, often progressive, and of delayed onset) was eliminated from Era 2, despite a concerning incidence of 40% in Era 1. Survival and neurocognitive outcomes after neonatal respiratory ECMO have not changed over 34 years.