Objective The clinical data of neonates with early-onset sepsis (EOS) were analyzed in order to explore the risk factors affecting neonatal early-onset sepsis associated acute kidney injury (AKI). Methods The clinical data of EOS neonates hospitalized in the neonatal ward from January 2018 to April 2022 were retrospectively analyzed. The neonates meeting the revised KDIGO AKI diagnostic criteria were assigned to AKI group, and the neonates without AKI were assigned to NAKI group according to 1:2 matching method. The clinical data between the two groups were compared to analyze the risk factors of neonatal early-onset sepsis complicated with acute kidney injury (ESA-AKI). Results A total of 70 neonates in the AKI group and 140 in the NAKI group were included in the study. A univariate conditional logistic regression analysis revealed that older admission age, maternal hypertension during pregnancy, asphyxia, high levels of serum urea nitrogen and creatinine at admission, coexisting with moderate to severe anemia, pulmonary hemorrhage, patent ductus arteriosus, septic shock, exposure to small doses of dopamine and meropenem, and surgery were risk factors for the development of AKI. The AKI group had a higher rate of death or abandonment (P<0.05). Conclusions AKI should be closely monitored in the group of neonates with EOS who were treated with dopamine, meropenem, and surgery and who had higher admission ages, asphyxia, maternal hypertension during pregnancy, high serum urea nitrogen and creatinine levels at admission, complicated by moderate to severe anemia, pulmonary hemorrhage, patent ductus arteriosus, and septic shock.