Background: Sepsis and septic shock are life-threatening causes of acute kidney injury (AKI) frequently seen and managed in intensive care units (ICUs). Sepsis-associated AKI (SA-AKI) independently contributes to the mortality of sepsis. Understanding the potential factors involved in kidney function recovery may further aid in the prevention and management of SA-AKI. This study aimed to describe the clinical characteristics of septic shock patients who required kidney replacement therapy and factors associated with kidney function recovery. Methods: We conducted a retrospective cohort study of adult septic shock patients who received in-hospital kidney replacement therapy at medical intensive care unit (MICU) at the Mayo Clinic, Rochester, from January 1, 2006, to May 31, 2018. Kidney function recovery was defined as liberation from kidney replacement therapy before hospital discharge. Associations between clinical features and kidney recovery were analyzed using multivariable Fine and Gray regression accounting for death as a competing event. Results: Our retrospective cohort consisted of 229 patients with a median (interquartile range [IQR]) age of 64 (52–74) years: 55% were men, 89% were Caucasians, 39% had diabetes mellitus (DM), 16% had heart failure, APACHE (Acute Physiology and Chronic Health Evaluation) III score was 105 (84–123), and SOFA (Sequential [Sepsis-related] Organ Failure Assessment) score was 12 (9–14). The patients received 1,567 (524–4,108) mL of intravenous fluids in the first 3 h, 92% required vasopressor support, and 83% required mechanical ventilation. The median MICU and hospital stays were 7 (4–13) and 19 (10–31) days, respectively. Median (IQR) kidney replacement therapy duration was 7 (3.5–17.1) days. Among 158 ICU survivors, 73 (46%) patients were weaned from RRT in ICU and 85 (54%) were transitioned to intermittent RRT. A higher volume of fluid resuscitation in the first 3 h (hazard ratio [HR] = 1.07 per 1 L, CI: 1.01–1.14, p = 0.04) and a history of DM (HR = 1.70, CI: 1.14–2.54, p = 0.009) were associated with kidney function recovery. Conclusion: Among septic shock patients who initiated kidney replacement therapy in the MICU, 41% recovered kidney function before discharge. A higher initial fluid resuscitation volume was associated with recovery, and interestingly, patients with DM had a higher chance of recovery.