Low soil fertility accompanied with inbalanced fertilizer application during crop cultivation in Ethiopia and Amhara Region adversely reduced crop yield and affected soil quality. As a result, the response of major crops to fertilizer applications is often by far below the attainable and potential yields. Thus, this study was conducted to identify the most yield limiting nutrients for sorghum (Sorghum bicolor) through omission trial in Raya Kobo district of Amhara Region during 2020/21 cropping season. The test crop was Girana one sorghum variety. The treatments included: Control (no fertilizer), NPS, PSBZn, NPBZn, NSBZn, NPSB, NPSZn, NPSBZn, recommended NP and NPSKBZn. The experiment was laid out in RCBD design with three replications. A composite soil sample at a depth of 0-20cm was collected before the application of the treatments to determine soil pH, soil texture, organic Carbon, CEC, Total N, available P, S, exchangeable K, Zn and B determination following standard procedures. Grain and stalk samples of sorghum were collected from each plot for analysis of N and P uptakes. Agronomic data were also collected following standard procedures. The collected data were subjected to analysis of variance using SAS version 9.0 software. The analysis of variance showed that significantly higher grain yield (4620 kg ha-1) was obtained from NPKSZnB, while the lowest grain yield (2759 kg ha-1) was obtained from the control followed by N omitted (2805 kg ha-1) plots. A significant yield reduction was observed in nitrogen fertilizer omitted plots than others and there was no statistically significant yield difference between potassium, sulfur, boron and zinc omitted plots and recommended NP plots. In addition to grain yield, the highest agronomic efficiency of N (20.2kg grain kg-1 N) and P(28.92kg grain kg-1 P2O5) were recorded from plots treated with NPKSZnB and recommended NP, respectively. As a result research and development should focus on nitrogen to attain optimum sorghum yield for the study area, Phosphorus could also applied to maintain the fertility level in the optimum range.