Abstract: Due to the limiting effects of drought on plant production, it is essential to find the most appropriate irrigation program that ensures efficient water use. Therefore, in this study, melon plants were exposed to different levels of water-deficit stress applied during the period of fruit development until harvest. A total of six different experimental treatments were established including full irrigation applied throughout the season (control—I100) and five different water-deficit stress regimes (I80, I60, I40, I20, and I0) corresponding to 80, 60, 40, 20, and 0% of water given to the S100 subject, respectively, during the fruit development stage until harvesting. The results revealed the variation in actual evapotranspiration (ETa) of the experimental subjects between 303.6 mm (I0) and 509.3 mm (I100), with decreased values as water stress increased. Water stress was found to cause significant decreases in yield and fruit characteristics. As water stress increases in melon, reactive oxygen species (ROS) are observed to increase, and accordingly, antioxidant activities against stress are observed to increase. The irrigation treatments that gave the best results in terms of RWC, stomatal conductance (gs), yield, and fruit characteristics of melon were I100 and I80. The findings revealed that the amount of irrigation water during the investigation period for melon cultivation can be reduced by 20% under the study conditions. However, it was observed that the period after fruit development is the most sensitive period to water stress in melon and that moderate and severe water stresses cause significant losses.