Graphene sheets were produced through chemical exfoliation of natural graphite flake and hydrazine conversion. Subsequently, graphene sheets were assembled into a thin film, and microscale liquid droplets were placed onto the film surface for measurement of wettability and contact angle. It is found that a graphene oxide sheet is hydrophilic and a graphene sheet is hydrophobic. Isolated graphene layers seem more difficult to wet in comparison to graphite, and low adhesion work was found in the graphene-liquid interface. Approximation of solid-liquid interfacial energy with the equation of state theory was applied to determine the graphene surface energy. The results indicate that surface energy of graphene and graphene oxide is 46.7 and 62.1 mJ/m2, respectively, while natural graphite flake shows asurface free energy of 54.8 mJ/m2 at room temperature. These results will provide valuable guidance for the design and manufacturing of graphene-based biomaterials, medical instruments, structural composites, electronics, and renewable energy devices.