Ethiopia is intensifying efforts to boost wheat production with effective nitrogen (N) andphosphorus (P) management. However, low soil fertility and the lack of recommendationson optimal N and P application rates remain major constraints limiting wheat production.The effects of different N and P nutrient rates on the yield and nutrient uptake of breadwheat were evaluated on Vertisols of Moretina Jiru District, North Shewa Zone, AmharaRegion, Ethiopia. The study was conducted using a factorial arrangement of treatments in Randomized Complete Block Design (RCBD) with three replications. The treatments werefive N rates (69, 115, 161, 207, and 253 kg ha -1 ), three phosphorus rates in the form of P 2 O 5 (46, 69, and 92 kg ha -1 ), and one control (0N- 0P 2 O 5 ) treatment. Data were collected on growth, yield parameters, nutrient uptake of N and P, soil sampling and analysis, and analyzed using R statistical software version 4.3. The results showed that wheat grain yieldwas highly significantly affected by N rates (p<0.001) and significantly (p<0.05) by P rates, with the highest grain yield being five times greater than the control. Applying N orP alone significantly increased wheat grain yield, but their interaction did not affect thegrain yield. The main effects of N and P, and their interaction, significantly influencednutrient use efficiency. Both higher N rates and the combined application of N and Pimproved P use efficiency. Application of 253 kg N ha -1 resulted in the highest grain yield(4891 kg ha -1 ), straw yield (6690 kg ha -1 ), soil plant analysis development (SPAD) value (47.96), total N uptake (113.50kg ha -1 ), total P uptake (44.12 kg ha -1 ) and protein content(10.82%) of wheat compared to the application of other N rates. The optimum P 2 rate was 69 kg P 2 O 5 ha -1 which resulted in the highest grain (3869 kg ha -1 ) and straw yields(5210 kg ha -1 ). Moreover, the economic analysis showed that the combined application of253 kg N with 69 kg P 2 O 5 ha -1 was profitable having the highest Benefit:Cost ratio value of3.60. Therefore, combined application of 253 kg N ha -1 and 69 kg P 2 was theoptimum rate and recommended for wheat production on Vertisols of Moretina Jirudistrict and similar agroecologies and moisture domains until further N rate is determined based on multilocation studies. O 5 ha -1 O 5