Non-specific adsorption of biomolecules (or “biofouling”) is a major problem in microfluidics and many other applications. The problem is particularly pernicious in digital microfluidics (DMF, a technique in which droplets are manipulated electrodynamically on an array of electrodes coated with a hydrophobic insulator), as local increases in surface energy that arise from fouling can cause droplet movement to fail. We report a new solution to this problem: a device coating bearing a combination of fluorinated poly(ethylene glycol) functionalities (FPEG) and perfluorinated methacrylate (FA) moieties. A range of different FPEG-FA copolymers were synthesized containing varying amounts of FPEG relative to the fluorinated backbone. Coatings with low%FPEG were found to result in significant reductions in protein adsorption and improvements in device lifetime (up to 5.5-fold) relative to the state of the art. An analysis of surface topology and chemistry suggests that FPEG-FA surfaces undergo a dynamic reconstruction upon activation by applying DMF driving potentials, with FPEG groups forming vertical protrusions out of the plane of the device surface. An analysis of changes in surface wettability and adhesion as a function of activation supports this hypothesis. This innovation represents an advance for digital microfluidics, and may also find use in other applications that are currently limited by biofouling.