The bio-agronomical response, along with the arsenic (As) translocation and partitioning were investigated in self-grafted melon "Proteo", or grafted onto three interspecific ("RS841", "Shintoza", and "Strong Tosa") and two intraspecific hybrids ("Dinero" and "Magnus"). Plants were grown in a soilless system and exposed to two As concentrations in the nutrient solution (0.002 and 3.80 mg L −1 , referred to as As− and As+) for 30 days. The As+ treatment lowered the aboveground dry biomass (−8%, on average), but the grafting combinations differed in terms of photosynthetic response. As regards the metalloid absorption, the rootstocks revealed a different tendency to uptake As into the root, where its concentration varied from 1633.57 to 369.10 mg kg −1 DW in "Magnus" and "RS841", respectively. The high bioaccumulation factors in root (ranging from 97.13 to 429.89) and the low translocation factors in shoot (from 0.015 to 0.071) and pulp (from 0.002 to 0.008) under As+, showed a high As mobility in the substrate-plant system, and a lower mobility inside the plants. This tendency was higher in the intraspecific rootstocks. Nonetheless, the interspecific "RS841" proved to be the best rootstock in maximizing yield and minimizing, at the same time, the As concentration into the fruit.