Topology is critical for properties and function of 2D nanomaterials. Membranes and films from 2D nanomaterials usually suffer from large tortuosity as a result from dense restacking of the nanosheets and thus have limited utility in applications such as electrodes for supercapacitor and batteries, which require ion transport through the nanosheet thickness. In comparison with conventional porous 2D nanomaterials, introducing holes through the nanosheets to create holey 2D nanomaterials with retention of the 2D-related properties is a more viable approach to improve molecular transport. Here, graphene is used as a model to study the fundamental structure-property relationship as a result from defect-enabled hole creation. Specifically, the correlation of electrochemical capacitive properties with structure and composition for holey graphene materials is prepared using a highly scalable controlled air oxidation process. The presence of holes on graphene sheets is not sufficient to account for the observed capacitance improvement. Rather, the improvement is achieved through the combination of an enhanced mesopore fraction with simultaneous oxygen doping while retaining the graphitic carbon network with minimal damage. The detailed understanding might be further applied to other 2D materials toward a broader range of both energy-related and other applications.