Pesticides aerial application may results in the drift to neighboring areas if some application technology is not well executed. This phenomenon should be minimized to reduce environmental risks and agricultural production costs. This work aimed to investigate the interaction of environmental conditions, surrounding distance, and application conditions influencing spray drift in aerial applications. Sampling data from aerial sprays were collected during three agricultural years (from 2012 to 2014) in fields cultivated with sorghum, millet, soybean, corn, and cotton. The following variables were evaluated: application swath width, application rate, distance from the applied field, wind speed, relative humidity, and temperature. The estimated Pearson’s correlations and path analysis identified that application rate and distance from the applied field and application were the variables that most influenced drift. Equations relating spray drift in function of distance from the applied field and application rate were adjusted in function of the variable, and a response surface model was constructed to estimate drift. The major pesticide class sprayed with aircraft in the Brazilian Cerrado was insecticide, followed by fungicide. This scenario shows the potential hazard risk of spray drift over the environment. The concentration of the drift deposits decreased as surrounding distance and application rate were increased. A mathematical equation of drift prediction was established, where the variables that contributed most to drift deposits were surrounding distance and wind speed. Thus, it is very important to monitor and respect the wind speed limits during the aerial spraying, mainly when there is any risk potential associated with pesticide exposure over the downwind direction.