Background: Sepsis is a life-threatening organ dysfunction, and acute kidney injury (AKI) is one of the most common complications of sepsis, as well as a cause of high mortality. This study aimed to determine the differences in the incidence of AKI, renal perfusion, clinical course, and outcome of septic patients with preserved or poor ejection admitted to the intensive care unit (ICU) of a tertiary care hospital. Materials and methods: This prospective, observational study included all consecutive patients admitted with septic shock to the ICU from March 2020 to November 2021. Index echocardiography was done within the first 6 hours of admission to the ICU. The vital hemodynamic parameters, dose of vasopressors, serum lactate, urine output, central venous pressure (CVP), and renal resistive index (RRI) were monitored at admission and 1, 6, 12, 24, and 48 hours following the start of vasopressors, with 0 hour being the time for initiation of vasopressors. Serum creatinine and sequential organ failure assessment (SOFA) scores were measured every day for 72 hours. Results: Among 50 adult patients, there were 17 patients with ejection fraction (EF) <40% (group I) and 33 patients with EF ≥40% (group II). The heart rate and CVP were higher in group I at baseline and at the start of vasopressor following fluid resuscitation. There was a significant difference in CVP between the groups at 0 hours, with mean CVP being higher in group I and this difference persisted for a few hours after the start of vasopressors (p = 0.02 at 1 hour and p = 0.2, nonsignificant at 6 hours). The difference in 28-day mortality was not significant between the groups (p = 0.62). The incidence of AKI between the two groups was 47% (eight patients) and 79% (26 patients), respectively, and the difference was statistically significant (p = 0.001). Around 35% of patients in group I had stage 3 AKI (six patients among eight); however, in group II, only 9% (three patients) were in stage 3 AKI. The higher incidence of AKI in group II was mainly contributed to patients in stages 1 and 2 of AKI. However, serum lactate was significantly higher in group II at 0 hours, and this difference persisted for 6 hours. While renal perfusion parameter, RRI, and urine output were comparable between the groups at 0 hours but showed decreasing trends earlier in group I. There was a significant decrease (p = 0.046) in RRI accompanied by an increase in urine output (p = 0.006) in group I patients with septic shock following initiation of dobutamine. Conclusion: Sepsis is associated with high mortality, but AKI in septic patients was not dependent on the cardiac status of the patient. The patients with preserved EF received vasopressors to achieve hemodynamic stability. Hence, we conclude that the early choice and dose of vasopressors might have a beneficial effect on renal perfusion and reduce the incidence of stage III AKI.