The evolution of copper-based interconnects requires the realization of an ultrathin diffusion barrier layer between the Cu interconnect and insulating layers. The present work reports the use of atomically thin layer graphene as a diffusion barrier to Cu metallization. The diffusion barrier performance is investigated by varying the grain size and thickness of the graphene layer; single-layer graphene of average grain size 2 ± 1 μm (denoted small-grain SLG), single-layer graphene of average grain size 10 ± 2 μm (denoted large-grain SLG), and multi-layer graphene (MLG) of thickness 5-10 nm. The thermal stability of these barriers is investigated after annealing Cu/small-grain SLG/Si, Cu/large-grain SLG/Si, and Cu/MLG/Si stacks at different temperatures ranging from 500 to 900 °C. X-ray diffraction, transmission electron microscopy, and time-of-flight secondary ion mass spectroscopy analyses confirm that the small-grain SLG barrier is stable after annealing up to 700 °C and that the large-grain SLG and MLG barriers are stable after annealing at 900 °C for 30 min under a mixed Ar and H2 gas atmosphere. The time-dependent dielectric breakdown (TDDB) test is used to evaluate graphene as a Cu diffusion barrier under real device operating conditions, revealing that both large-grain SLG and MLG have excellent barrier performance, while small-grain SLG fails quickly. Notably, the large-grain SLG acts as a better diffusion barrier than the thicker MLG in the TDDB test, indicating that the grain boundary density of a graphene diffusion barrier is more important than its thickness. The near-zero-thickness SLG serves as a promising Cu diffusion barrier for advanced metallization.