Formation and evolution of fluid overpressure is critical to the generation, migration, and accumulation of natural gas. However, one aspect of this process that has received little attention so far is how and why fluid overpressure in shales is either preserved or dissipated. Here, we investigate the generation and preservation of fluid overpressure in different parts of the Wufeng–Longmaxi shales, southeastern Sichuan Basin, China. These rocks represent a good test case to understand preservation versus loss of overpressure because different drill holes into the same stratigraphic unit variably show present-day conditions of either normal (approximately hydrostatic) pressure or significant overpressures (exceeding hydrostatic). The question is, in the case of the presently normally pressured shales, did these rocks never experience fluid overpressure, or did overpressure develop but then dissipate? And, if the latter, then when and why was pressure lost? We report detailed evidence that both the presently overpressured and normally pressured shales consistently record an early (120–106 Ma) stage of high fluid overpressure, >70% of the lithostatic load, caused by gas generation during deep burial. The pressure regime then later diverged during subsequent uplift, as the currently normally pressured rocks underwent faster pressure release because of rapid uplift during the late Yanshanian Orogeny, whereas the presently overpressured rocks experienced more gradual uplift that favored preservation of high fluid pressures. Our results demonstrate that the fluid inclusions hosted in shale fracture veins directly record the fluid pressure changes in shale layers, providing more intuitive insight into the dynamic evolution of shale gas generation and accumulation.