In electronic transport, umklapp processes play a fundamental role as the only intrinsic mechanism that allows electrons to transfer momentum to the crystal lattice and, therefore, provide a finite electrical resistance in pure metals1,2. However, umklapp scattering is difficult to demonstrate in experiment, as it is easily obscured by other dissipation mechanisms1–6. Here we show that electron–electron umklapp scattering dominates the transport properties of graphene-on-boron-nitride superlattices over a wide range of temperature and carrier density. The umklapp processes cause giant excess resistivity that rapidly increases with increasing superlattice period and are responsible for deterioration of the room-temperature mobility by more than an order of magnitude as compared to standard, non-superlattice graphene devices. The umklapp scattering exhibits a quadratic temperature dependence accompanied by a pronounced electron–hole asymmetry with the effect being much stronger for holes than electrons. In addition to being of fundamental interest, our results have direct implications for design of possible electronic devices based on heterostructures featuring superlattices. © 2018, The Author(s), under exclusive licence to Springer Nature Limited.