A field experiment was conducted to identify the most yield limiting nutrients for wheat yield on Nitisols of D/Eliase District North western Ethiopia during 2021/22 main cropping season. The experiments were laid out in a completely randomized block design (RCBD) each with three replications. The treatments were control, NP, PKSZnB (-N), NKSZnB (-P), NPSZnB (-K), NPKZnB (-S), NPKSZn (-B), NPKSB (-Zn) and full fertilization (+NPKSZnB). The available data were collected and subjected to ANOVA using SAS 9.3 software. The LSD test was used to separate means at 5% level of significance. According to the results obtained, considerable reduced in plant height, spike length, grain and biomass yield was recorded due to omission of N and P nutrients compared with fully fertilized plots. The highest yield reduction was recorded due to omission of N followed by P in the study district. The highest grain yield of wheat (2835.20kgha<sup>-1</sup>) was measured from recommended NP fertilized plots while the lowest grain yields (357.50kgha<sup>-1</sup> and 545.90kgha<sup>-1</sup>) were obtained from the control and N omitted plots respectively. Therefore, N and P were found to be the most yield limiting nutrients for wheat production indicating that the inherent N and P supplying capacity of soil is very low. Thus, N and P nutrients should be applied in optimum dose for efficient nutrient uptake which ultimately increases wheat productivity. The highest agronomic efficiency (19.08 kg grain/kg nutrient applied) was recorded from plots treated with recommended NP fertilizer. In addition the highest profits realized with application of recommended NP fertilizer compared with other treatments The economics of wheat cultivation therefore indicates that omission of (-N) and (-P) nutrients results in losses. Omission of nitrogen (-N) followed by omission of phosphorus (-P) has more impact on wheat yield and profits in the study area.