<b><i>Background:</i></b> Critically ill neonates are at high risk of kidney injury, mainly in the first days of life. Acute kidney injury (AKI) may be underdiagnosed due to lack of a uniform definition. In addition, long-term renal follow-up is limited. <b><i>Objective:</i></b> To describe incidence, etiology, and outcome of neonates developing AKI within the first week after birth in a cohort of NICU-admitted neonates between 2008 and 2018. Renal function at discharge in infants with early AKI was assessed. <b><i>Methods and Subjects:</i></b> AKI was defined as an absolute serum Cr (sCr) value above 1.5 mg/dL (132 μmol/L) after the first 24 h or as stage 2–3 of the NIDDK neonatal definition. Clinical data and outcomes were collected from medical records and retrospectively analyzed. <b><i>Results:</i></b> From January 2008 to December 2018, a total of 9,376 infants were admitted to the NICU of Wilhelmina Children’s Hospital/UMC Utrecht, of whom 139 were diagnosed with AKI during the first week after birth. In 72 term infants, the most common etiology was perinatal asphyxia (72.2%), followed by congenital kidney and urinary tract malformations (CAKUT) (8.3%), congenital heart disease (6.9%), and sepsis (2.8%). Associated conditions in 67 preterm infants were medical treatment of a hemodynamic significant PDA (27.2%), ­CAKUT (21%), and birth asphyxia (19.4%). Among preterm neonates and neonates with perinatal asphyxia, AKI was mainly diagnosed by the sCr &#x3e;1.5 mg/dL criterion. Renal function at discharge improved in 76 neonates with AKI associated with acquired conditions. Neonates with stage 3 AKI showed increased sCr values at discharge. Half of these were caused by congenital kidney malformations and evolved into chronic kidney disease (CKD) later in life. Neurodevelopmental outcome (NDO) at 2 years was favorable in 93% of surviving neonates with detailed follow-up. <b><i>Conclusion:</i></b> During the first week after birth, AKI was seen in 1.5% of infants admitted to a level III NICU. Renal function at discharge had improved in most neonates with acquired AKI but not in infants diagnosed with stage 3 AKI. Long-term renal function needs further exploration, whereas NDO appears to be good.