Abiotic environmental stress factors and their combinations significantly reduce the growth, yield, and grain quality of wheat. An important role is played by the use of environmentally oriented and safe approaches that improve growth and productivity by inducing the natural defence mechanisms of the plant hostile stress factors and/or their combinations. Here, we studied the effect of pre-sowing seed treatment with beneficial bacterial endophytes Bacillus subtilis (strains 10-4 and 26D) on growth, tolerance, and yield of two wheat genotypes (Triticum aestivum L., drought tolerant (DT) cv. Ekada70; drought susceptible (DS) cv. Salavat Yulaev) under combined herbicide+drought stress (HDS) conditions. Combined stress was simulated in the 17-day-old wheat seedlings grown as soil culture under controlled conditions by spraying with the herbicide Sekator Turbo (Bayer, Germany). 3 days later the seedlings were subjected to drought stress by stopping irrigating for 7 days (until the severe water deficit was reached), followed by 4 days of recovery with a normal irrigation regime. It was found that exposure to combined HDS inhibited plant growth, reduced leaf photosynthetic pigments chlorophyll (Chl) a and Chl b, leaf area as well as increased lipid peroxidation (LPO) of cell membranes. Wherein, the degree of damages was most pronounced for DS cv. Salavat Yulaev. Pre-treatment with B. subtilis 10-4 and 26D prevented such HDS-caused adverse influences on plant growth, leaf area, photosynthetic pigments, and membrane integrity (i.e., malondialdehyde (MDA)-a marker of LPO) as well as contributed to faster recovery of plants after restoration of normal watering in comparison with nonbacterial-treated control. Exposure to HDS for 7 days during the tillering phase led to the formation of lower height plants with a shortened ear, yield per ear, and the presence of deformed ears in comparing to unstressed control plants were observed. While the plants pre-treated with B. subtilis 10-4 and 26D under the same stress conditions were characterized by formation of normal ear, an increased plant height, productive stems number, and grain yield in comparison with nonbacterial-treated control. Thus, the results indicate the effectiveness of pre-sowing seed treatment with endophytic B. subtilis 10-4 and 26D as a bio-safe strategy to improve wheat growth and tolerance under combined HDS conditions and more rapid restore of plant growth and photosynthetic activity in the post-stress period, which ultimately manifests in better yield formation.