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Lack of high-quality irrigation water and soil salinity are two main environmental factors that affect plant development. When both stressors are combined, the soil becomes sterile and constrains plant productivity. Consequently, two field trials were designed to assess whether plant growth-promoting microbes (PGPMs; <i>Bradyrhizobium japonicum</i> (USDA 110) and <i>Trichoderma harzianum</i>) and potassium humate (K-humate) can stimulate soybean growth, productivity, and seed quality under two different watering regimes as follows: (i) well-watered (WW), where plants were irrigated at 12-day intervals (recommended), and (ii) water stress (WS), where plants were irrigated at the 18-day intervals in salt-affected soil during 2020 and 2021 seasons. Results revealed that coupled application of PGPMs and K-humate resulted in a substantial improvement in K⁺ levels in the leaves compared to Na⁺ levels, which has a direct positive impact on an enhancement in the antioxidants defense system (CAT, POX, SOD), which caused the decline of the oxidative stress indicators (H₂O₂, MDA, and EL%) as well as proline content under water stress in salt-affected soil. Hence, a significant increase in root length, nodule weight, soybean relative water content (RWC), stomatal conductance, photosynthetic pigments, net photosynthetic rate, soluble protein, seed carbohydrate content as well as the number of pods plant⁻¹ and seed yield was reported. In conclusion, the combined application of PGPMs and K-humate might be recommended to maximize the soybean growth and productivity under harsh growth conditions (e.g., water stress and soil salinity).