Drought is a major challenge for agriculture worldwide, being one of the main causes of losses in plant production. Various studies reported that some soil's bacteria can improve plant tolerance to environmental stresses by the enhancement of water and nutrient uptake by plants. The Atacama Desert in Chile, the driest place on earth, harbors a largely unexplored microbial richness. This study aimed to evaluate the ability of various sp. from the hyper arid Atacama Desert in the improvement in tolerance to drought stress in lettuce ( L. var. capitata, cv. "Super Milanesa") plants. Seven strains of spp. were isolated from the rhizosphere of the Chilean endemic plants and , and then identified using the 16s rRNA gene. Indole acetic acid (IAA) production, phosphate solubilization, nitrogen fixation, and 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase activity were assessed. Lettuce plants were inoculated with spp. strains and subjected to two different irrigation conditions (95% and 45% of field capacity) and their biomass, net photosynthesis, relative water content, photosynthetic pigments, nitrogen and phosphorus uptake, oxidative damage, proline production, and phenolic compounds were evaluated. The results indicated that plants inoculated with , , and demonstrated the highest growth under drought conditions compared to non-inoculated plants. Treatments increased biomass production and were strongly associated with enhanced N-uptake, water status, chlorophyll content, and photosynthetic activity. Our results show that specific species from the Atacama Desert enhance drought stress tolerance in lettuce plants by promoting several beneficial plant traits that facilitate water absorption and nutrient uptake, which support the use of this unexplored and unexploited natural resource as potent bioinoculants to improve plant production under increasing drought conditions.