This study aimed to evaluate the effects of plant growth-promoting Rhizobacteria (PGPR) treatments, B1, Azosprillium lipoferum Sp2 and B2, A. lipoferum Sp2 + Pseudomonas sp. SARS12, as well as inorganic nitrogen doses (60, 100, 140 and 180 kg N ha–1) on some soil physical characters, physiological, anatomical and yield parameters as well as nitrogen use efficiency (NUE) of wheat under water deficit stress. Results showed that water stress significantly decreased physiological characters such as chlorophyll content (6.7 and 9.8%) and relative water content (13.7 and 11.2%) in both seasons, respectively. Nevertheless, proline and malondialdehyde (MDA) were increased significantly (26.9, 12.3% and 90.2, 96.4%) in both seasons, respectively, as signals for water stress. The anatomical characteristics of flag leaves were negatively affected. Inoculation of wheat grains with PGPR significantly increased field capacity and RWC, adjusted enzymes’ activity and thus improved the physiological and yield traits and NUE as well as improving the anatomical features of flag leaves. Moreover, the combination of integrated PGPR and 140 kg N ha−1 significantly improved grain yield and its components as well as grain N uptake in comparison to control treatments. In conclusion, PGPR improved wheat productivity and NUE; they are an eco-friendly and cost-effective approach for improving plant production, and reducing nutrient leaching hazards and the negative impact of water stress.