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Hyperleukocytosis in acute myeloid leukemia (AML) could cause life-threatening complications, including leukostasis and tumor lysis syndrome (TLS). While leukocytapheresis and continuous renal replacement therapy (CRRT) are typically performed independently to maintain hemodynamic stability and manage anticoagulation, their simultaneous application is rarely reported. We report a case of a deteriorating patient with secondary AML treated with simultaneous leukocytapheresis and CRRT. For the CRRT circuit, two separate hemodialysis catheters were placed in the femoral vein (access) and internal jugular vein (return). The leukocytapheresis circuit was then connected to the CRRT return line. The procedure was completed without immediate bleeding or thrombotic complications. Reductions in white blood cell counts, ammonia, and lactic acid levels were observed, along with improved oxygenation. Simultaneous leukocytapheresis and CRRT can be a safe and effective modality for the urgent management of hyperleukocytosis and TLS in critically ill patients.