Our knowledge of graft partner interactions is very limited. We profiled the metabolome of eleven graft combination in leaves, stems, and phloem exudate from both above and below the graft union 5–6 months after grafting and compared them. This revealed that (1) grafting has a minor impact on the metabolome of grafted grapevines when tissues and genotypes were compared, (2) heterografting affects rootstocks more than scions, (3) the presence of a heterologous grafting partner increases defense-related compounds in both scion and rootstocks in shorter and longer distances from the graft, and (4) leaves were revealed as the best tissue to search for grafting-related metabolic markers.