Salinity is one of the serious abiotic stresses adversely affecting the productivity of most crops. Arbuscular mycorrhizal fungi and salicylic acid treatments are known to ameliorate salinity stress, but their combined effect has never been examined on watermelon. Therefore, to investigate the synergetic effects of them on vegetative growth, nutrient content, physiological and biochemical characteristics, and fruit yield and quality of watermelon cv. Aswan F1 grown under saline water conditions, a split split-plot design with three replications was conducted in the North Sinai Governorate, Egypt, during the two successive growing seasons of 2020 and 2021. The main factor included irrigation water salinity regimes at three levels: 1600, 4000 and 5000 ppm. Subfactors included arbuscular mycorrhizal fungi at two levels (non-inoculated and inoculated), and salicylic acid foliar spraying at four concentrations (0, 1, 2 and 4 mM) in subplots. The results revealed that saline water increasing led to evident reductions in vegetative growth parameters and fruit yield. Mycorrhizal inoculation or foliar application of salicylic acid improved the growth and productivity of watermelon plants under salinity conditions by maintaining a higher leaf relative water content and membrane stability index, enhancing chlorophyll content, and inducing the accumulation of proline and the activity of antioxidant enzymes. In addition, this study affirmed the synergistic effects of mycorrhizal inoculation and salicylic acid spraying on ameliorating the deleterious effects of saline-water irrigation on the growth and productivity of watermelon plants via generating simulative impacts on all physiological and biochemical attributes.