In order to evaluate the response of grain yield, yield compounds, quality and water use efficiency of barley cv. Giza 126 cultivar to irrigation water regimes and biofertilization inoculation, field experiment was conducted in the Experimental Farm of Maryout Experimental Station, Desert Research Center, Egypt, during two successive growing seasons 2017/18 and 2018/19. The experimental design was a split plot, whereas the main plots involved by irrigation water regimes and the sub-main plots involved by biofertilization treatments, with three replicates. The obtained results indicated that yield, yield attributes and N, P and K contents in grains of barley i.e. plant height, spike length, number of spikes/m2, number of grains/spike, 1000-grain weight, grain yield ha-1. The contents of nitrogen, phosphorus percentage in barley grains and water use efficiency significantly increased with increasing irrigation water applications and by biofertilizers treatments. However, the number of spikelets/spike, and potassium percentage in grains was not significantly affected by irrigations water regimes and/or biofertilizers treatments. Water use efficiency (kg m-3) for grain yield significantly increased with increasing irrigation water application with biofertilizers treatments in the two growing seasons. The highest values of all studded traits were recorded by applying the three times irrigation in the two seasons. Regarding biofertilizers inoculation effects, results showed that the maximum values of most studied traits were recorded by inoculating with both Mycorrhiza and Azotobacter together as a combination treatment for both seasons except plant height, which produced highest values, by inoculating with Mycorrhiza and Azotobacter in the first season and by using Azotobacter alone in the second one. On the other side, maximum value of nitrogen percentage in grains were recorded by treating the plant with Azotobacter alone in the two seasons. The results clearly showed that barley plants which irrigated by the three irrigations and inoculated by Mycorrhiza and Azotobacter together, as a combination treatment, produced the highest yield, yield components and water use efficiency at the North Western Coast of Egypt.