This study was carried out to determine the optimum nitrogen and phosphorus rates for achieving optimum yields and nutrient use efficiency for wheat in highlands of Eastern Uganda. An on station randomized complete block design experiment was conducted at Buginyanya Zonal Agricultural Research and Development Institute. Two varieties Fahari and Pasa were treated with four levels of nitrogen (0, 30, 60, & 90 kg ha-1) and three levels of phosphorus (0, 7.5 &15 kg ha-1). The fertilizer treatments were each replicated three times. The highest grain yield of Pasa and Fahari was 3211kg ha-1, 2726 kg ha-1 respectively obtained at a nutrient combination of 60 kg N ha-1 and 15 P kg ha-1. The same nutrient combination resulted into highest number of tillers: (Pasa 4 and Fahari 5), kernel per spike of 40 for Pasa and 32 for Fahari. Maximum total kernel weight, spike length and plant height were obtained at 90 kg N ha-1 and 7.5 kg P ha-1 nutrient combinations. Pasa produced a significantly higher Agronomic Nitrogen Use Efficiency and Agronomic Phosphorus Use Efficiency obtained at 30 kg N ha-1 and 7.5 kg P ha-1 nutrient combinations, compared to Fahari at the same N and P rates. Optimum N and P fertilizer combination for best grain yield of both wheat varieties tested is 60 kg N ha-1 and 15 kg P ha-1 combinations.