Optimum nitrogen (N) fertilizer application is important for agronomic, economic, and environmental reasons. Among different N management tools, active crop canopy sensors are a recent and promising tool widely evaluated for use in corn but still under-evaluated for use in winter wheat. The objective of this study was to determine whether vegetation indices derived from in-season active crop canopy sensor data can be used to predict winter wheat grain yield and protein content and subsequently recommend nitrogen management. We conducted field experiments at four different research stations across Nebraska in 2018/2019 and 2019/2020. We recorded crop canopy reflectance data at early growth stage (Feekes 6.0) and late growth stage (Feekes 10.5.3), calculated two vegetation indices: Normalized Difference Vegetation Index (NDVI) and Normalized Difference Red Edge (NDRE) from reflectance data, and did regression analysis for the vegetation indices versus soil available N, yield, and protein. Our results show that both NDVI and NDRE at Feekes 6.0 had a significant linear relationship with soil available nitrogen (R² = 0.25; p = 0.01 and R² = 0.42; p = 0.004, respectively). We also found that grain yield had a significant linear relationship with NDVI at Feekes 6.0 (R² = 0.287; p = 0.002) and with NDRE at Feekes 10.5.3 (R² = 0.543; p = 0.006). Furthermore, grain protein had significant linear relationships with NDVI and NDRE at Feekes 10.5.3 (R² = 0.603; p < 0.001 and R² = 0.265; p = 0.004, respectively) and with NDVI, but only at Feekes 6 (R² = 0.737; p < 0.001). These results indicate that NDVI and NDRE are correlated with soil available nitrogen, grain yield, and grain protein. However, the strength of relation varies based on growth stage and type of vegetation index. Our findings suggest that active crop canopy sensor derived NDRE can potentially be used for assessing crop nitrogen status and predicting grain yield while NDVI can be used for predicting grain protein, ultimately leading to better nitrogen management practices.