Applying the optimum rate of fertilizer nitrogen (N) is a critical factor for field management. Multispectral information collected by active canopy sensors can potentially indicate the leaf N status and aid in predicting grain yield. Crop Circle multispectral data were acquired with the purpose of measuring the reflectance data to calculate vegetation indices (VIs) at different growth stages. Applying the optimum rate of fertilizer N can have a considerable impact on grain yield and profitability. The objectives of this study were to evaluate the reliability of a handheld Crop Circle ACS-430, to estimate corn leaf N concentration and predict grain yield of corn using machine learning (ML) models. The analysis was conducted using four ML models to identify the best prediction model for measurements acquired with a Crop Circle ACS-430 field sensor at three growth stages. Four fertilizer N levels from deficient to excessive in 50/50 spilt were applied to corn at 1–2 leaves, with visible leaf collars (V1–V2 stage) and at the V6–V7 stage to establish widely varying N nutritional status. Crop Circle spectral observations were used to derive 25 VIs for different growth stages (V4, V6, and VT) of corn at the W. B. Andrews Agricultural Systems farm of Mississippi State University. Multispectral raw data, along with Vis, were used to quantify leaf N status and predict the yield of corn. In addition, the accuracy of wavelength-based and VI-based models were compared to examine the best model inputs. Due to limited observed data, the stratification approach was used to split data to train and test set to obtain balanced data for each stage. Repeated cross validation (RCV) was then used to train the models. Results showed that the Simplified Canopy Chlorophyll Content Index (SCCCI) and Red-edge ratio vegetation index (RERVI) were the most effective VIs for estimating leaf N% and that SCCCI, Red-edge chlorophyll index (CIRE), RERVI, Soil Adjusted Vegetation Index (SAVI), and Normalized Difference Vegetation Index (NDVI) were ...