In this article, the effects of high-energy proton irradiation on top-gate graphene field-effect transistors (GFETs) were investigated by using 20 MeV protons. The basic electrical parameters of the top-gate GFETs were measured before and after proton irradiation with a fluence of 1 × 1011 p/cm2 and 5 × 1011 p/cm2, respectively. Decreased saturation current, increased Dirac sheet resistance, and negative drift in the Dirac voltage in response to proton irradiation were observed. According to the transfer characteristic curves, it was found that the carrier mobility was reduced after proton irradiation. The analysis suggests that proton irradiation generates a large net positive charge in the gate oxide layer, which induces a negative drift in the Dirac voltage. Introducing defects and increased impurities at the gate oxide/graphene interface after proton irradiation resulted in enhanced Coulomb scattering and reduced mobility of the carriers, which in turn affects the Dirac sheet resistance and saturation current. After annealing at room temperature, the electrical characteristics of the devices were partially restored. The results of the technical computer-aided design (TCAD) simulation indicate that the reduction in carrier mobility is the main reason for the degradation of the electrical performance of the device. Monte Carlo simulations were conducted to determine the ionization and nonionization energy losses induced by proton incidence in top-gate GFET devices. The simulation data show that the ionization energy loss is the primary cause of the degradation of the electrical performance.