Objective To define those children who develop acute kidney injury (AKI) within 48 h of admission from the emergency department (ED) and ascertain patient-related factors in the ED associated with AKI. Methods Retrospective, cohort study of children, birth to 19 years, admitted to a tertiary pediatric hospital from the ED between January 2010 and December 2013 who had serum creatinine (SCr) drawn as part of clinical care. AKI was defined as a 50% increase in SCr above baseline, as measured within 48 h of hospital presentation. Multivariable logistic regression was performed to determine factors associated with AKI by comparing those with and without kidney injury on hospital presentation. Results Of all ED admissions, 13,827 subjects (27%) were included; 10% developed AKI. Of kids with AKI, 75% had a measured SCr consistent with AKI while in the ED, 36% were admitted to the intensive care unit, and 2% died (all significantly more than children without AKI). Young age, history of AKI or solid organ transplant, receipt of intravenous fluids or central venous access in the ED, and admission to intensive care were factors independently associated with AKI (AUC = 0.793, 95% CI 0.78–0.81). Conclusions One in 10 children who had SCr measured and were admitted to a tertiary pediatric hospital had AKI on or within 48 h of presentation. Inherent characteristics, identifiable in the ED, are associated with an increased risk of AKI. Future research should focus on improving AKI recognition in the ED by the development of a risk stratification tool.