It is shown that the performance of graphene diffusion barriers can be enhanced by stacking multiple layers of graphene and increasing grain size. The focus is on large-area barriers of graphene grown by chemical vapor deposition (CVD) in the context of passivating an underlying Cu substrate from oxidation in air at 200 °C and use imaging Raman spectroscopy as a tool to temporally and spatially map the barrier performance and to guide barrier design. At 200 °C in air, Cu oxidation proceeds in multiple regimes: first slowly via transport through atomic-scale grain boundary defects inherent to CVD-graphene and then more rapidly as the graphene itself degrades and new defects are formed. In the initial regime, the graphene passivates better than previously reported. Whereas oxidation through single sheets primarily occurs through grain boundaries, oxidation through multiple sheets is spatially confined to their intersection. Performance further increases with grain-size. The degradation of the graphene itself at 200 °C ultimately limits high temperature but suggests superior low temperature barrier performance. This study is expected to improve the understanding of mass transport through CVD-graphene materials and lead to improved large area graphene materials for barrier applications.