Agricultural productivity was negatively impacted by low soil fertility and uneven fertilizer application during crop cultivation in Ethiopia. Because of this, important crops frequently respond to fertilizer applications significantly below their achievable and potential yields. This study was carried out to determine the most sorghum yield-limiting nutrients in the Raya Kobo area of the Amhara Region in the 2020/21 crop season. Sorghum variety Girana-One was used as the test crop. Control, NPS, PSBZn, NPBZn, NSBZn, NPSB, NPSZn, NPSBZn, recommended NP, and NPSKBZn were treatments. Three replications of the experiment were used in a randomized complete block design. Before treatment application, a composite soil sample was collected at a depth of 0–20 cm to determine the soil’s physicochemical properties. To evaluate N and P uptakes, samples of sorghum stalk and grain were collected. SAS software was used to analyze the data. Results showed that, NPKSZnB produced a considerably greater grain yield (4620 kg·ha−1), whereas the control and N omitted plots produced the lowest grain yields (2759 kg·ha−1) and 2805 kg·ha−1, respectively. Nitrogen fertilizer missing plots showed a statistically significant yield drop compared to the other plots, and there was no statistically significant yield difference between the prescribed NP plots and the potassium, sulfur, boron, or zinc omitted plots. The plots treated with NPKSZnB had the highest agronomic efficiency for N (19.7 kg grain kg−1·N) and P (10.6 kg grain kg−1 P2O5). Therefore, research and development should therefore concentrate on nitrogen to achieve the best sorghum yield for the study location. Phosphorus might also be used to keep the fertility level within the ideal range.