Atomic layer deposition (ALD) is the method of choice to obtain uniform insulating films on graphene for device applications. Owing to the lack of out-of-plane bonds in the sp2 lattice of graphene, nucleation of ALD layers is typically promoted by functionalization treatments or predeposition of a seed layer, which, in turn, can adversely affect graphene electrical properties. Hence, ALD of dielectrics on graphene without prefunctionalization and seed layers would be highly desirable. In this work, uniform Al2O3 films are obtained by seed-layer-free thermal ALD at 250 °C on highly homogeneous monolayer (1L) epitaxial graphene (EG) (>98% 1L coverage) grown on on-axis 4H-SiC(0001). The enhanced nucleation behavior on 1L graphene is not related to the SiC substrate, but it is peculiar of the EG/SiC interface. Ab initio calculations show an enhanced adsorption energy for water molecules on highly n-type doped 1L graphene, indicating the high doping of EG induced by the underlying buffer layer as the origin of the excellent Al2O3 nucleation. Nanoscale current mapping by conductive atomic force microscopy shows excellent insulating properties of the Al2O3 thin films on 1L EG, with a breakdown field > 8 MV cm−1. These results will have important impact in graphene device technology.