Foxtail millet is highly valued in China; however, its optimal fertilization parameters are unknown. This study investigated the effects of nitrogen (N), phosphorus (P), and potassium (K) fertilizer combinations on foxtail millet agronomic traits, photosynthetic characteristics, yield, and quality to promote rational fertilizer application. Pot experiments were conducted using the “3414” fertilizer effect scheme and the representative crop variety was JG21, containing four NPK levels and 20 replicates per treatment, individually. The effects of N, P, and K levels on agronomic traits were analyzed during the jointing, heading, and filling stages. JG21 performed optimally under treatment with N160P90K150 (T6); the yield and fat content increased by 49.32% and 13% compared to the control. Correlation analysis revealed that N was significantly positively (negatively) correlated with the protein (amylose) content. P was significantly positively correlated with the fat and moisture content and K was correlated with the moisture, fat, and protein content, but was negatively with the amylose content. Overall, rational ratios of NPK fertilization improved foxtail millet yield and quality. Based on fuzzy comprehensive evaluation, the T6 treatment (N160P90K150) demonstrated the highest comprehensive effect among 13 NPK fertilizer combinations. Rational application of NPK in foxtail millet may improve agronomic performance by enhancing leaf photosynthetic efficiency and aboveground biomass accumulation.