Quantum friction has been shown to dominate the singular behavior of nanoscale water flows, especially for water-graphene systems of keen current interest. In contrast to classical friction resulting solely from the surface properties of solids, we here show that the quantum friction at water-graphene interface is non-additively amplified by the practically required substrate through a newly developed method at an ab initio level. The amplification of quantum friction reaches one order of magnitude for AB-stacked bilayer graphene and up to four orders of magnitude for monolayer graphene on Ni(111) substrate; the latter surpasses the cumulative friction of isolated graphene and Ni(111) by twenty times. The interfacial electronic interaction between graphene and substrate, not the electrostatic coupling, is revealed to serve as the primary driver of the friction amplification. These findings suggest substrate engineering as a transformative strategy to tune friction at fluid-solid interfaces without surface modification.