BackgroundThe heavy use of conventional mineral fertilization considerably increased wheat growth and yield components. However, the excessive nitrogen fertilization accounts for large expenses on farmers’ budget and has negative environmental drawbacks to soil and water ecosystems. Recently, establishing wheat plants associations with a variety of N2-fixing cyanobacteria and/or growth promoting microorganisms in farming systems as nutrients source is seen as ecofriendly and economically feasible solution.ResultsIn this work, the influence of different nitrogen (N) levels (100% N, 75% N, and 50% N as urea) and cyanobacteria (Cy) and/or yeast (Y) inoculation each alone or both in combination with different nitrogen levels were assessed on two different wheat (Triticumae stivum L.) genotypes (Sids-14 and Giza-171) through field experiments over two consecutive seasons (2019/2020 and 2020/2021). Although, the full recommended dose (FRD) (100% N) showed the highest chlorophyll (Chl) a, b content during tillering stage, grains quality (NPK-uptake, protein%), and wheat yield components in both genotypes. The integrated inoculation of cyanobacteria and yeast with 50% N, 75% N-fertilization enhanced wheat growth characteristic (Chl a,b) and upgraded soil microbial community (nitrogenase activity and CO2 evolution) in Sids-14 and Giza-171. Cy combined with Y and partial N-fertilization levels enhanced NPK-uptake Kg/fed and protein% in wheat grains in the two wheat genotypes. Moreover, this combination recorded a wheat yield components (plant height, number of spikes/m2, number of grains/spike, 1000 grains wt (gm) and grains yield (tonne/fed) insignificantly different from those obtained by FRD in wheat cultivation.ConclusionThe integrated application of cyanobacteria with yeast and 50% N or 75% N-fertilization improved soil fertility index and promoted NPK- uptake, protein% and wheat yield components, showing comparable values to conventional chemical fertilization. Cyanobacteria combined with yeast inoculation had socio-economic benefits as it can save about 25–50% of the required mineral nitrogen fertilizers for wheat crop production.