This study used hyperspectral reflectance data to evaluate the crop physiological parameters of sweet maize. Principal component analysis (PCA) was applied to identify the wavelengths that primarily contributed to each selected PC. Correlation analysis and multiple linear regression, with a stepwise algorithm, were used to select the best-performing vegetation indices (VIs) for monitoring the yield and physiological response of sweet maize grown under different water and nitrogen availability. The spectral reflectance measurements of crops were taken during the mid-season stage, for two consecutive growing seasons. The multivariate regression results showed that red-edge group indices, such as CARI (Chlorophyll Absorption Reflectance Index), DD (Double Difference Index), REIP (Red-Edge Inflection Point), and Clred-edge (Chlorophyll Red-Edge) indices were good predictors of yield and physiological parameters, confirming the crucial role of the red-edge spectral region that also emerged through PCA. Moreover, DD, REIP, and Clred-edge VIs were able to discriminate transient temporary stress at the mid-season stage, as well as to separate water and N stress levels. Therefore, hyperspectral reflectance VIs can provide valid information to growers, helping them identify and discriminate between different stress conditions.