The natural ventilation model plays a crucial role in greenhouse environmental control. It has been extensively studied by previous researchers, but it is limited to low-altitude areas. This study established a numerical model of single-span plastic greenhouses in high-altitude areas. The model was validated using measured data, showing a good agreement between the measured and simulated values. By setting boundary conditions based on on-site monitoring data, ventilation rates were extracted under different conditions for numerical simulations. Through nonlinear fitting, an empirical formula for natural ventilation rates, with a determination coefficient (R²) of 0.9724, was derived. The formula was validated through an energy balance analysis of indoor air. Different ventilation opening sizes were simulated to derive an empirical formula for natural ventilation rates based on opening size. Building on this, the relationship between plant height and ventilation rate was analyzed. As the dominant factors of natural ventilation change with environmental fluctuations, this study also proposed the threshold wind speed for wind pressure ventilation, thermal pressure ventilation, and coupled ventilation, filling the knowledge gap in relevant ventilation rate calculations. This is the first time that a natural ventilation model of single-span plastic greenhouses in high-altitude areas has been proposed, providing the basis in terms of modeling for the further development of local facility agriculture.