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Background To assess whether acute kidney injury (AKI) is independently associated with hospital mortality in ICU patients with sepsis, and estimate the excess AKI-related mortality attributable to AKI. Methods We analyzed adult patients from two distinct retrospective critically ill cohorts: (1) Medical Information Mart for Intensive Care IV (MIMIC IV; n = 15,610) cohort and (2) Wenzhou (n = 1,341) cohort. AKI was defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We applied multivariate logistic and linear regression models to assess the hospital and ICU mortality, hospital length-of-stay (LOS), and ICU LOS. The excess attributable mortality for AKI in ICU patients with sepsis was further evaluated. Results AKI occurred in 5,225 subjects in the MIMIC IV cohort (33.5%) and 494 in the Wenzhou cohort (36.8%). Each stage of AKI was an independent risk factor for hospital mortality in multivariate logistic regression after adjusting for baseline illness severity. The excess attributable mortality for AKI was 58.6% (95% CI [46.8%–70.3%]) in MIMIC IV and 44.6% (95% CI [12.7%–76.4%]) in Wenzhou. Additionally, AKI was independently associated with increased ICU mortality, hospital LOS, and ICU LOS. Conclusion Acute kidney injury is an independent risk factor for hospital and ICU mortality, as well as hospital and ICU LOS in critically ill patients with sepsis. Thus, AKI is associated with excess attributable mortality.