In arid and semi-arid regions, plant responses to water deficits at different phenological stages should be investigated for efficient use of water resources and sustainable irrigation management. This study was conducted under the regional conditions in the Konya province with a semi-arid climate for two years (2016–17) to determine the effects of irrigation applied at different growth stages on yield and quality traits of melon (Cucumis melo L. cv. Dardanos). Thus, a total of eight different irrigation treatments were implemented at three different growth stages of melon (from planting to flowering (V), flowering to fruit swelling (F), and fruit swelling to harvesting (M)). These treatments were specified as single-stage irrigation (V, F, and M), two-stage irrigation (VF, VM, and FM), irrigation for the whole season (VFM–stress-free), and non-irrigated. The seasonal total water consumption varied between 129.7 and 418.5 mm in 2016 and between 161.8 and 428.6 mm in 2017. The greatest fruit yield (52.9 t/ha) was obtained from stress-free VFM treatment; however, significant decreases were observed in fruit yields for other treatments. When yield and quality traits were assessed together, principal component analysis (PCA) revealed that VF and FM treatments had similar values to VFM treatment. With regard to irrigation water productivity (IWP), there were no significant differences between VM and VFM treatments, and VM treatment provided about 47% water saving. On the other hand, significant decreases were observed in fruit yields of V, F, and M treatments, in which irrigation and the water stress were applied during only a single phenological stage and the other two periods, respectively. Since the yield response factor (ky) for the whole growing season of melon was greater than 1.0 (1.30), the melon was considered sensitive to water stress under semi-arid climatic conditions. In conclusion, two-stage irrigation treatments (VF, VM, and FM) could be applied in well-scheduled irrigation programs of melon for efficient use of water resources and sustainable irrigation management in arid and semi-arid regions.