Graphite oxide (GO) shares the same structural features of graphite, except by the presence of randomly distributed oxygenated functional groups. In this work, we investigate the effect of the annealing under high pressures on the structure of GO, using a combination of different characterization techniques and atomistic computational simulations. GO samples were submitted to different pressures (ambient, 2.5 and 7.7 GPa) and temperatures (up to 1500°C) using a toroidal high pressure chamber. Reactive molecular dynamics (MD) simulations of the process were carried out to provide some insight on the structural transformations induced on GO.  Ex-situ characterization of the processed samples shows that high pressure increased the interaction among the functional groups, inducing their elimination as gas molecules and a consequent reduction of the interlayer spacing to values closer to those exhibited by turbostratic graphite. The samples processed at ambient pressure consisted of relatively large sheets of reduced GO, containing defects in the structure. In contrast, the morphology of the samples processed at higher pressures and temperatures is similar to those of graphite nanocrystals (significantly smaller than the pristine GO sheets). The simulations results corroborate with these observations, and help to explain the reasons for the differences in the morphology of the material when submitted to different conditions. They show that the application of higher pressures leads to a significant reduction on the volume within the planes, inhibiting the formation of gas molecules and their diffusion throughout the material. The reactions among the graphitic matrix and the formed gases along with the surface diffusion of O atoms lead to the concentration of functional groups in specific regions, resulting in the etching of C atoms and local tearing of the structure, which eventually leads to the formation of crystalline nanodomains observed in the experiments.