This prospective randomized controlled trial aimed to compare the effects of sevoflurane and propofol anesthesia on the occurrence of acute kidney injury (AKI) following lung transplantation (LTx) surgery. Sixty adult patients undergoing bilateral LTx were randomized to receive either inhalation of sevoflurane or continuous infusion of propofol for general anesthesia. The primary outcomes were AKI incidence according to the Acute Kidney Injury Network (AKIN) criteria and blood biomarker of kidney injury, including neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C levels within 48 h of surgery. Serum interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and superoxide dismutase were measured before and after surgery. The post-operative 30-day morbidity and long-term mortality were also assessed. Significantly fewer patients in the propofol group developed AKI compared with the sevoflurane group (13% vs. 38%, = 0.030). NGAL levels were significantly lower in the propofol group at immediately after, 24 h, and 48 h post-operation. IL-6 levels were significantly lower in the propofol group immediately after surgery. AKI occurrence was significantly associated with a lower 5-year survival rate. Total intravenous anesthesia with propofol reduced the AKI incidence in LTx compared with sevoflurane, which is understood to be mediated by the attenuation of inflammatory responses.