Early detection of plant diseases, prior to symptom development, can allow for targeted and more proactive disease management. The objective of this study was to evaluate the use of near-infrared (NIR) spectroscopy combined with machine learning for early detection of rice sheath blight (ShB), caused by the fungus Rhizoctonia solani. We collected NIR spectra from leaves of ShBsusceptible rice (Oryza sativa L.) cultivar, Lemont, growing in a growth chamber one day following inoculation with R. solani, and prior to the development of any disease symptoms. Support vector machine (SVM) and random forest, two machine learning algorithms, were used to build and evaluate the accuracy of supervised classification-based disease predictive models. Sparse partial least squares discriminant analysis was used to confirm the results. The most accurate model comparing mock-inoculated and inoculated plants was SVM-based and had an overall testing accuracy of 86.1% (N = 72), while when control, mock-inoculated, and inoculated plants were compared the most accurate SVM model had an overall testing accuracy of 73.3% (N = 105). These results suggest that machine learning models could be developed into tools to diagnose infected but asymptomatic plants based on spectral profiles at the early stages of disease development. While testing and validation in field trials are still needed, this technique holds promise for application in the field for disease diagnosis and management.