Axillary and subclavian artery cannulation for veno-arterial extracorporeal membrane oxygenation (V-A ECMO) offers clinical advantages but introduces complex flow dynamics within the aortic arch. This study employed patient-specific computational fluid dynamics (CFD) models derived from 10 computed tomography (CT)-based geometries to simulate ECMO flow via either the right axillary artery or left axillary artery access under varying levels of cardiac dysfunction. Three distinct flow behaviors were observed—descending-directed, arch-split, and retrograde aortic valve (AV)-directed patterns—depending on access site, support level, and aortic geometry. Right axillary artery access more frequently resulted in retrograde flow, particularly in type III arch configurations. In contrast, left axillary artery cannulation promoted antegrade or arch-split flow, independent of arch morphology. These findings suggest that left axillary artery access may provide more favorable antegrade flow hemodynamics in V-A ECMO, particularly when native cardiac output is impaired. Computational fluid dynamics modeling offers valuable insights to guide individualized cannulation strategies based on patient anatomy and cardiac function.