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Identifying nematode damage in large soybean areas is not always achievable in a practical way. Multispectral reflectance sensors have not been thoroughly evaluated to detect nematode damage in soybeans (Glycine max L.). The main research aims of this study were to: (i) determine the bivariate relationship between individual spectral bands and vegetation indices (VIs) relative to soybean conditions (symptomatic versus asymptomatic), and (ii) to select the best model for identifying plant conditions using three algorithms (logistic regression—LR, random forest—RF, conditional inference tree—CIT) and three options for data input using bands, vegetation indices (VIs), and bands plus VIs. The trial was conducted in Brazil on three on-farm soybean fields presenting different species of nematode infestation. Multispectral imagery was obtained using a drone-mounted MicaSense RedEdge^® sensor. At each sampling, georeferenced point nematode infestation and spectral measurements of soybean plants were retrieved for the classification of symptomatic and asymptomatic areas, according to the threshold level adopted. Bivariate analysis of variance (ANOVA), LR, RF, and CIT were used to select the multispectral bands/VIs that discriminated among symptomatic and asymptomatic plants, assessing the best model via their respective parameters for accuracy, sensitivity, and specificity. The greatest classification accuracy (>0.70) was achieved when using the CIT algorithm with the spectral bands only, with green (560 ± 20 nm) and near-infrared (840 ± 40 nm) included as the main spectral input variables in the model. These results demonstrate …