In nature, plants are constantly exposed to a varied abiotic and biotic stresses or their combinations, limiting the productivity of major crops, including wheat. Combinations of drought and soil-borneFusarium-instigated diseases are the most common combinations of stresses, significantly reducing wheat yield around the world. Here, were analyzed the potential of application of endophytic bacteriaBacillus subtilis(strain 10-4) together with the natural signal molecule salicylic acid (SA) to improve growth and tolerance ofTriticum aestivumL. (wheat) plants under combined drought andFusarium culmorum-instigated root rot (FRR) stresses. It was revealed that pre-sowing treatment withB. subtilis10-4, SA, andB. subtilis10-4 + SA, both under normal and combined drought conditions, notably reduced (by 50-80% or more) the incidence of FRR development in wheat plants, with the most notable effect forB. subtilis10-4 + SA (wherein disease symptoms were almost absent). Moreover,B. subtilis10-4, SA, and especiallyB. subtilis10-4 + SA increased plant growth (root and shoot length, fresh and dry biomass) under normal (up to 20-50%), drought (up to 15-40%), FRR (up to 15-30%), and combined drought + FRR stresses (up to 20%), with the maximum effect forB. subtilis10-4 + SA. Additionally,B. subtilis10-4, SA, andB. subtilis10-4 + SA decreased stress (drought, FRR, and combined drought + FRR)-instigated lipid peroxidation and osmotic damages of plant cells. The findings indicate that endophytic bacteriaB. subtilis10-4 alone and in a mixture with SA may be used as an effective eco-friendly agent to improve wheat growth and tolerance under the influence of drought, FRR, and combinations of these stresses.