This study assessed the potential of Bacillus endophyticus PB3, Bacillus altitudinis PB46, and Bacillus megaterium PB50 to induce drought tolerance in a susceptible rice cultivar. The leaves of the potted rice plants subjected to physical drought stress for 10 days during the flowering stage were inoculated with single-strain suspensions. Control pots of irrigated and drought-stressed plants were included in the experiment for comparison. In all treatments, the plant stress-related physiochemical and biochemical changes were examined and the expression of six stress-responsive genes in rice leaves was evaluated. The colonization potential on the surface of the rice leaves and stomata of the most successful strain in terms of induced tolerance was confirmed in the gnotobiotic experiment. The plants sprayed with B. megaterium PB50 showed an elevated stress tolerance based on their higher relative water content and increased contents of total sugars, proteins, proline, phenolics, potassium, calcium, abscisic acid, and indole acetic acid, as well as a high expression of stress-related genes ( LEA , RAB16B , HSP70 , SNAC1 , and bZIP23 ). Moreover, this strain improved yield parameters compared to other treatments and also confirmed its leaf surface colonization. Overall, this study indicates that the foliar application of B. megaterium PB50 can induce tolerance to drought stress in rice.