Abstract The objective of this study is to investigate the seasonal performance characteristics of novel ejector-expansion air conditioners (EEACs) with low global warming potential refrigerants. A simplified simulation model for EEACs is developed and validated using measured data. Using a simulation model, the coefficient of performance, cooling seasonal performance factor, and life cycle climate performance of the EEACs employing low global warming potential refrigerants are analyzed at various operating conditions and modes. In addition, the climatic effects on the cooling seasonal performance factors and life cycle climate performances of the EEACs are evaluated at four different weather conditions. The EEAC with R290 exhibits the cooling seasonal performance factor and total CO2 emissions that are 22% higher and 23.3% lower, respectively, than those of the baseline air conditioner with R410A. In general, R290 is the best working fluid for EEACs in terms of the seasonal performance and lifetime environmental factor.