A field experiment was conducted at the Faculty of Agriculture, Kafr El-Sheikh University, Egypt, during the 2021/22 and 2022/23 growing seasons, to investigate the effects of mineral nitrogen fertilization and Bio-fertilizers inoculation on wheat (Triticum aestivum L.). Using a randomized complete block design (RCBD) in a split-split plot design with three replications, the study examined two wheat cultivars (Sids 14 and Sakha 95) allocated to the main plots, four nitrogen levels (25, 50, 75 and 100 kg N fed.-1) in the sub plots and Bio-fertilizer inoculation with (Azotobacter sp. , Azospirillum sp. and without inoculation) in the sub-sub plots. Results showed a strong positive relationship between increased nitrogen fertilization and Bio-fertilizer inoculation to improve in plant height(cm), fertile tillers, grains spike-1, 1000-grain weight, grain yield(ton fed.-1), biological yield(ton fed.-1), straw yield(ton fed.-1), chlorophyll content and grain protein content(%). Sakha 95 consistently outperformed Sids 14 in all measured traits. The study concluded that results indicated 75 or 100 kg N with inoculation recorded the highest grain yield with Sakha 95 and the results obtained that the combining higher nitrogen rates with Bio-fertilizer inoculation significantly enhances wheat yield and quality in clay loam soils.