As a key parameter for describing the microscopic characteristics of fuel spray, the Sauter mean diameter (SMD) is widely applied for evaluating the spray effect. Researchers have proposed several formulas for predicting the SMD under different experimental conditions. However, there are two main limitations. First, only the physical properties of the fuel and initial injection parameters are considered; the effect of airflow on SMD is not considered. Second, the spray affected by airflow disperses more widely and causes the SMD to vary in different regions. Hence, the global SMD calculated by these formulas cannot adequately describe the droplet size distribution in each region of the spray under cross flow conditions. In this study, the droplet velocity and diameter were measured using a particle image analysis experimental system in different spray regions under cross flow conditions. The relationship between SMD and fuel properties, cross flow speed, droplet velocity, and injection conditions were analyzed. Moreover, the prediction formulas for multi-zone SMD were proposed that can calculate the SMD in different regions of the fuel spray under cross flow conditions.