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Nitrogen (N), phosphorus (P), and potassium (K) exert various effects on adzuki bean yields. Our research was conducted in a semi-arid area, and four test sites were established in environments that have chernozem or sandy loam soils. During a five-year period, the effects of N, P, and K fertilizers on yield were comprehensively investigated in field trials (2014–2016) and for model-implementation trials (2017–2018), with models established prior to the latter. In the field trials, 23 treatments comprising different N, P, and K combinations significantly affected both yield and yield components, and regression analysis indicated that the experimental results were suitable for model establishment. The model subsequently demonstrated that the yield and the yield components were more sensitive to N and K fertilizer than to P fertilizer. Moreover, the yield and yield components increased. These yield increases were intense in response to the 0.5 to 1.34 levels in terms of the single effects; interaction effects; and the effects of combinations of N, P, and K fertilizers. Moreover, the effects of combinations of N, P, and K fertilizers were more significant on yield than were the single or interaction effects of N, P, and K fertilizers. The optimal fertilizer combination that resulted in high yields (≥1941.53 kg ha−1) comprised 57.23–68.43 kg ha−1 N, 36.04–47.32 kg ha−1 P2O5 and 50.29–61.27 kg ha−1 K2O. The fertilizer combination that resulted in the maximum yield was 62.98 kg ha−1 N, 47.04 kg ha−1 P2O5 and 59.95 kg ha−1 K2O (N:P2O5:K2O = 1:0.75:0.95), which produced the model-expected yield in trials at multiple sites. An economical fertilizer combination was determined on the basis of the best fertilizer measures in consideration of the cost of fertilizer and seed; this combination achieved yields of 2236.17 kg ha−1, the profit was 15,653.16 Yuan ha−1, and the corresponding rates were 57.60 kg ha−1 N, 47.03 kg ha−1 P2O5, and 31.64 kg ha−1 K2O (N:P2O5:K2O = 1:0.82:0.55). [ABSTRACT FROM AUTHOR]