Owing to the increased global warming, drought severity has increased in many regions, threatening food security, especially in arid and semi-arid areas. Therefore, it is imperative to mitigate the impact of drought on plants in water-stressed areas. The utilization of plant-growth-promoting rhizobacteria (PGPRs) serves as an environmentally friendly approach to enhance the resilience of plants exposed to abiotic stress, specifically drought. This research focuses on examining the effects of 35 PGPR isolates, possessing significant ACC (1-aminocyclopropane-1-carboxylic acid) deaminase activity, which were obtained from diverse plant-rhizosphere soil samples encompassing approximately 17,000 km2 of semi-arid regions. The investigation was conducted on watermelon plants experiencing varying degrees of water stress (30% and 60% water stress). An increase in water stress exerted a detrimental effect on agro-morphological parameters, such as biomass (root + shoot), leaf number, and leaf area of non-inoculated plants. PGPRs stimulated plant growth and increased water use efficiency, especially under severe water-stress (60% water stress) conditions compared to non inoculated plants (control). Furthermore, some PGPRs such as B7, B22, B26 and B28 supported carotenoid synthesis, which plays an important role in photosynthesis, whereas some alleviated the effect of water stress in watermelon plants by stimulating the antioxidant defense system. The outcomes of principal component, where the data were collectively assessed, demonstrated the superior efficacy of certain PGPRs. Specifically, under water-stress conditions, PGPR isolates B31, B32, and B35 exhibited significant growth-promoting effects on watermelon. Additionally, isolates B13 and B15 demonstrated the activation of antioxidant defense mechanisms, including proline, catalase, and peroxidase. PGPRs showed considerable results on the agro-morphological, physiological, and biochemical properties of watermelon under 60% water-stress conditions compared with those under 30% water stress. In conclusion, PGPRs promoted growth and alleviated severe water stress in watermelon plants compared to their control. The results of this study elucidate PGPR-triggered response mechanisms in water-stressed watermelon plants.