Stratified air distribution systems are commonly used in large space buildings. The research on the airflow organization of stratified air conditioners is deficient in terms of the analysis of multivariable factors. Moreover, studies on the coupled operation of stratified air conditioners and natural ventilation are few. In this paper, taking a Shanghai Airport Terminal departure hall for the study, air distribution and thermal comfort of the cross-section at a height of 1.6 m are simulated and compared under different working conditions, and the effect of natural ventilation coupling operation is studied. The results show that the air distribution is the most uniform and the thermal comfort is the best (predicted mean vote is 0.428, predicted percentage of dissatisfaction is 15.2%) when the working conditions are 5.9% air supply speed, 11 °C cooling temperature difference and 0° air supply angle. With the coupled operation of natural ventilation, the thermal comfort can be improved from Grade II to Grade I.