Drought is one of the most important abiotic factors that restrict the production of agricultural plants. An effective way to avoid the negative effects of drought on crops is to cultivate high-yielding varieties by grafting them onto drought-tolerant rootstocks with a strong root system. For this purpose, five different plant materials were used: wild watermelon rootstock, i.e., wild watermelon (A1 and A2), open-pollinated Lagenaria siceraria (gourd) rootstocks (A3), Cucurbita maxima Duchesne × Cucurbita moschata Duchesne (TZ-148) F1 watermelon rootstocks (A4), and the ungrafted control. Five different irrigation depths were applied considering irrigation water (IW)/cumulative pan evaporation (CPE) rations (I100: 1.0 IW/CPE, I75:0.75 IW/CPE, I50:0.50 IW/CPE, I35:0.35 IW/CPE, and I0:rain-fed). The results showed that the use of rootstock and water stress increased the rate of sugar content in the fruit. The highest positive relationship was found between glucose and total sugar, whereas the highest negative relationship was observed between sucrose and malic acid. Parameters such as glucose, total sugar, and citric acid showed significant changes in drought stress. Fructose and malic acid showed significant differences between the rootstocks. Principal Component Analysis (PCA) revealed that the A2I50 application was located in the positive region of both components and showed important results in these parameters. The TZ148 rootstock contributed significantly to the quality of watermelon. In addition, the A2 wild watermelon rootstock showed respectable results, especially under water stress conditions. Based on these results, we conclude that the use of wild watermelon rootstock will contribute to the fruit quality in arid and semi-arid areas with limited water resources.