To evaluate the potential of natural refrigerants CO₂ and R290 for replacing R134a in thermal management systems, a high-precision dynamic vehicle-level model encompassing the cabin, battery, and powertrain was developed on a simulation platform. The thermal management performance of systems using these refrigerants was systematically evaluated under the China Light-Duty Vehicle Test Cycle (CLTC). During dynamic operation, the motor power was significantly correlated with speed variations, whereas the power of the TMS was more stable. In cooling conditions, R290 had an energy efficiency advantage over CO₂, with a smaller thermal management energy consumption factor (TMEF). However, at extreme high temperatures of 40°C and 45°C, the TMEF of the R290 system exceeded that of the CO₂ system. In heating conditions, CO₂ TMS has an outstanding energy efficiency advantage. At ambient temperatures of 0°C and 7°C, the TMEF of all three systems were essentially equivalent. When the ambient temperature dropped below -10°C, the R290 system performed better than the R134a system. Besides, as the ambient temperature decreased, the advantage of the CO₂ system over the R290 system continued to increase. Therefore, CO₂ has a performance advantage in cold or extremely hot regions, while R290 is more suitable for mildly hot regions. These analyses provide important guidance for low-carbon and efficient refrigerant substitution in thermal management for electric vehicles.