Fusarium rot is one of the main postharvest diseases of melons, directly interfering with the quality and commercial use of the fruit. The purpose of this study was to assess the effect of environmental factors (temperature, pH and salinity) and the pathogenicity of four Fusarium species (F. falciforme, F. kalimantanense, F. pernambucanum and F. sulawesiense) belonging to three different species complexes on disease development on melon, as well as the in vitro and in vivo sensitivity of these species to the fungicides azoxystrobin + fludioxonil, imazalil and thiabendazole. The results showed optimum fungal growth temperatures from 24.5 to 27.2°C, and optimum pH from 6.10 to 8.37 for all Fusarium species. NaCl concentrations (250–1000 mM) significantly reduced in vitro mycelial growth for all isolates. All species were pathogenic to melon plants and fruit, with an isolate of F. falciforme being the most aggressive, causing the highest disease severity in plants and fruit (43.3% and 62.5%, respectively). The isolate of F. sulawesiense tested showed high in vitro sensitivity to two fungicides (azoxystrobin + fludioxonil and imazalil), with EC50 values below 1 mg/L of a.i. Fruit inoculated with the selected isolates of F. falciforme and F. pernambucanum showed a reduction in the disease severity on the peduncle when treated with the fungicide thiabendazole (9.0% and 4.0%, respectively). Azoxystrobin + fludioxonil was responsible for the lowest disease severity in the epicarp caused by the same isolates (0.0% and 2.5%, respectively). These results are relevant to improve management strategies for diseases of melon caused by Fusarium spp.