The estimation of physicochemical crop parameters based on spectral indices depend strongly on planting year, cultivar, and growing period. Therefore, the efficient monitoring of crop growth and nitrogen (N) fertilizer treatment requires that we develop a generic spectral index that allows the rapid assessment of the plant nitrogen content (PNC) of crops and that is independent of year, cultivar, and growing period. Thus, to obtain the best indicator for estimating potato PNC, herein, we provide an in-depth comparative analysis of the use of hyperspectral single-band reflectance and two- and three-band spectral indices of arbitrary bands for estimating potato PNC over several years and for different cultivars and growth periods. Potato field trials under different N treatments were conducted over the years 2018 and 2019. An unmanned aerial vehicle hyperspectral remote sensing platform was used to acquire canopy reflectance data at several key potato growth periods, and six spectral transformation techniques and 12 arbitrary band combinations were constructed. From these, optimal single-, two-, and three-dimensional spectral indices were selected. Finally, each optimal spectral index was used to estimate potato PNC under different scenarios and the results were systematically evaluated based on a correlation analysis and univariate linear modeling. The results show that, although the spectral transformation technique strengthens the correlation between spectral information and potato PNC, the PNC estimation model constructed based on single-band reflectance is of limited accuracy and stability. In contrast, the optimal three-band spectral index TBI 5 (530,734,514) performs optimally, with coefficients of determination of 0.67 and 0.65, root mean square errors of 0.39 and 0.39, and normalized root mean square errors of 12.64% and 12.17% for the calibration and validation datasets, respectively. The results thus provide a reference for the rapid and efficient monitoring of PNC in large potato fields.