Traditional disease severity monitoring is subjective and inefficient. This study employs a Parrot multispectral sensor mounted on an unmanned aerial vehicle (UAV) to apply machine learning algorithms, such as random forest, for categorizing defoliation levels in R7-stage soybean plants. This research assesses the effectiveness of vegetation indices, spectral bands, and relative vegetation cover as input parameters, demonstrating that machine learning approaches combined with multispectral imagery can provide a more accurate and efficient assessment of Asian soybean rust in commercial soybean fields. The random forest algorithm exhibited satisfactory classification performance when compared to recent studies, achieving accuracy, precision, recall, F1-score, specificity, and AUC values of 0.94, 0.92, 0.92, 0.92, 0.97, and 0.97, respectively. The input variables identified as most important for the classification model were the WDRVI and MPRI indices, the red-edge and NIR bands, and relative vegetation cover, with the highest Gini importance index.