Because of the low viscosity of high-water-based fluids, the intense wear and leakage of key friction pairs represent a bottleneck to the wide application of the high-water-based hydraulic motor in engineering machinery. In this work, based on the common characteristics of plane friction pairs, the friction experiments of a 316L stainless steel (316L)–polytetrafluoroethylene (PTFE) friction pair under various working condition were carried out by a self-designed friction experimental system with fluid lubrication. The influence of lubrication pressure and surface morphology on the 316L–PTFE friction pair was investigated both experimentally and theoretically. The experimental and numerical results indicated that increasing lubrication pressure reduced the surface wear of PTFE sample, but the leakage of 316L–PTFE friction pair also increased. It could not form an effective fluid lubrication film in the 316L–PTFE friction pair under low lubrication pressure, which caused the severe wear in friction pair interface. The smooth 316L surface could be conducive to the formation of high-water-based fluid lubrication film in 316L–PTFE friction interface. The pressure distribution of high-water-based fluid lubrication film in 316L–PTFE friction pair was also obtained in fluent. The PTFE surface was easily worn when the lubrication film in the friction pair was too thin or uneven. The friction and wear were obviously improved when the normal load was balanced by the bearing capacity of the high-water-based fluid lubrication film.