Background Neurocognitive dysfunction is a known complication in children with chronic kidney disease (CKD). However, less is known about putative mechanisms or modifiable risk factors. The objective of this study was to characterize and determine risk factors for cognitive dysfunction in children, adolescents, and young adults with CKD compared with controls. Study Design Cross-sectional study. Setting & Participants The Neurocognitive Assessment and Magnetic Resonance Imaging Analysis of Children and Young Adults With Chronic Kidney Disease (NiCK) Study included 90 individuals aged 8 to 25 years with CKD compared with 70 controls. Predictors CKD versus control, estimated glomerular filtration rate (eGFR), ambulatory blood pressure. Outcomes Performance on neurocognitive assessment with relevant tests grouped into 11 domains defined a priori by expert opinion. Results of tests were converted to age-normalized z scores. Measurements Each neurocognitive domain was analyzed through linear regression, adjusting for eGFR and demographic and clinical variables. For domains defined by multiple tests, the median z score of tests in that domain was used. Results We found significantly poorer performance in multiple areas of neurocognitive function among individuals with CKD compared with controls. Particular deficits were seen in domains related to attention, memory, and inhibitory control. Adjusted for demographic and clinical factors, we found lower performance in multiple domains with decreasing eGFRs (attention: β = 0.053, P = 0.02; visual spatial: β = 0.062, P = 0.02; and visual working memory: β = 0.069, P = 0.04). Increased diastolic load and decreased diastolic nocturnal dipping on ambulatory blood pressure monitoring were independently associated with impairments in neurocognitive performance. Limitations Unable to assess changes in neurocognitive function over time, and neurocognitive tests were grouped into predetermined neurocognitive domains. Conclusions Lower eGFR in children, adolescents, and young adults is associated with poorer neurocognitive performance, particularly in areas of attention, memory, and inhibitory control. Hypertension identified on ambulatory blood pressure monitoring may be an important risk factor, illustrating that neurocognitive function is an area of target-organ damage in CKD.