We present a technique to precisely measure the surface energies between two-dimensional materials and substrates that is simple to implement and allows exploration of spatial and chemical control of adhesion at the nanoscale. As an example, we characterize the delamination of single-layer graphene from monolayers of pyrene tethered to glass in water and maximize the work of separation between these surfaces by varying the density of pyrene groups in the monolayer. Control of this energy scale enables high-fidelity graphene-transfer protocols that can resist failure under sonication. Additionally, we find that the work required for graphene peeling and readhesion exhibits a dramatic rate-independent hysteresis, differing by a factor of 100. This work establishes a rational means to control the adhesion of 2D materials and enables a systematic approach to engineer stimuli-responsive adhesives and mechanical technologies at the nanoscale. © 2017 American Chemical Society.