Commercial cucurbits such as cucumber, melon and watermelon are commonly grafted onto interspecific Cucurbita hybrid rootstocks to increase yield and mange soil-borne diseases. This study conducted in private farm in Qallien district in Kafr El-Sheikh Governorate northern Egypt during the period from 2018 to 2020 to identify local Fusarium wilt-resistant interspecific Cucurbita hybrid rootstocks which provide high grafting compatibility with hybrid cucumber scions. Results revealed that disease severity percentage in all interspecific hybrids (0 to 45%) was significantly lower than susceptible commercial cucumber Junco F₁ (73.4%). Seven out of the 20 individual hybrids (A02, B02, D02, F01, G02, H01 and I02) were resistant or highly resistant to Fusarium wilt with a mean disease severity ≤ 25%. Results from the greenhouse trials confirmed high levels of resistance in three interspecific hybrids (G02, H01 and I02) which were used as rootstocks for cucumber Junco F₁. Fruit yield parameters were increased significantly in grafted cucumber Junco F₁ onto wilt-resistant interspecific hybrids compared to un-grafted cucumber. Highly significant differences in anatomical structure were observed between wilt-resistant interspecific hybrid rootstock H01 and susceptible check Junco F₁. Fruit yield parameters of grafted cucumber Junco F₁ were negatively correlated with disease severity. The interspecific hybrids evaluated in the present study could be promising rootstocks to increase productivity and manage soil-borne diseases for commercial production of major cucurbits in Egypt.