Background Cardiac surgery-associated acute kidney injury (CS-AKI) is common, but its impact on clinical outcomes is variable. Parsing AKI into sub-phenotype(s) and integrating pathologic positive cumulative fluid balance (CFB) may better inform prognosis. We sought to determine whether durational sub-phenotyping of CS-AKI with CFB strengthens association with outcomes among neonates undergoing the Norwood procedure. Methods Multicenter, retrospective cohort study from the Neonatal and Pediatric Heart and Renal Outcomes Network. Transient CS-AKI: present only on post-operative day (POD) 1 and/or 2; persistent CS-AKI: continued after POD 2. CFB was evaluated per day and peak CFB during the first 7 postoperative days. Primary and secondary outcomes were mortality, respiratory support-free and hospital-free days (at 28, 60 days, respectively). The primary predictor was persistent CS-AKI, defined by modified neonatal Kidney Disease: Improving Global Outcomes criteria. Results CS-AKI occurred in 59% (205/347) neonates: 36.6% (127/347) transient and 22.5% (78/347) persistent; CFB > 10% occurred in 18.7% (65/347). Patients with either persistent CS-AKI or peak CFB > 10% had higher mortality. Combined persistent CS-AKI with peak CFB > 10% ( n  = 21) associated with increased mortality (aOR: 7.8, 95% CI: 1.4, 45.5; p  = 0.02), decreased respiratory support-free (predicted mean 12 vs. 19; p  < 0.001) and hospital-free days (17 vs. 29; p  = 0.048) compared to those with neither. Conclusions The combination of persistent CS-AKI and peak CFB > 10% after the Norwood procedure is associated with mortality and hospital resource utilization. Prospective studies targeting intra- and postoperative CS-AKI risk factors and reducing CFB have the potential to improve outcomes. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information