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In a specific area, fertilizer application for a crop depends on the soil type and profitability. Optimizing chemical fertilizer utilization in crop production is crucial from an environmental and economic point of view. However, there is limited information available on the optimum NPSB fertilizer rate for the production of wheat and barley in the study area. Thus, the study aimed to establish area-specific NPSB (18.9% N, 16.44% P, 6.95% S, and 0.1% B) blended fertilizer rate recommendations for the optimal grain yield and profitability of wheat and barley. The field experiment was conducted in two locations in the 2021 and 2022 cropping seasons using a randomized complete block design with three replications. The nine treatments included 0, 25, 50, 75, 100, 125, 150, 175, and 200 kg ha−1 NPSB fertilizer rates. Growth, yield, and yield component data in wheat and barley were collected from randomly selected individual plants and the net plot area. An economic analysis was conducted for grain yield using the procedure established by the International Maize and Wheat Improvement Center. The analysis of variance results showed that blended fertilizer significantly (p < 0.01) affected plant height, number of productive tillers, spike length, number of kernels, thousand seed weight, biomass yield, grain yield, and harvest index traits. The application of a 150 kg ha−1 NPSB rate produced the highest grain yield (5419.0 kg ha−1) in wheat, whereas the application of a 125 kg ha−1 NPSB rate gave the maximum grain yield (4708.0 kg ha−1) in food barley. The economic analysis revealed that the application of a 150 kg ha−1 NPSB fertilizer rate for wheat gave the highest net benefits (309711.50 ETB ha−1) and marginal rate of return (MRR) (4096.96%), while the application of a 125 kg ha−1 NPSB fertilizer rate for barley obtained the highest net benefits (184424.00 ETB ha−1) and MRR (2195.39%). Therefore, to optimize the productivity and profitability of wheat and barley in the study area and similar agroecologies, farmers are recommended to use 150 kg ha⁻¹ NPSB for wheat and 125 kg ha⁻¹ NPSB for barley.