Macrophomina phaseolina is the causal agent of charcoal rot disease, which attacks many plant species, including those in the Cucurbitaceae. The fungus is frequently isolated from wilted melon and watermelon plants in Israel. Nevertheless, the role of M. phaseolina in disease progress and induction of wilting or yield reduction in watermelons and melons is not clear and not similar. Precise disease identification is important in order to suggest effective control measures. The objective of the current study was therefore to investigate disease progress and document its damage in watermelon and melon. Watermelons and melons were seeded in a field naturally infested with M. phaseolina and in the greenhouse in 10-L pots containing dune sand. Plants were inoculated at 35 days of age using two methods: drenching with macerated fungus around the crown area or stabbing the lower stem with an M. phaseolina-infested toothpick. Disease progress was documented in the field and in the greenhouse. Plant colonization and symptom development were more pronounced in melon than in watermelon. Large lesions and significant internal rotting developed in melon plants inoculated by the two methods in both field and greenhouse. In watermelon, however, no lesions or internal rotting were observed. Disease effect on melons and watermelons was observed only in the field, a short time before harvest, and was expressed as partial wilting and significant loss of shoot and fruit fresh weight similarly to disease appearance under natural infection. No wilting of melons or watermelons was observed in the greenhouse experiment.