We conducted high-velocity friction experiments on clay-rich fault gouge taken from the megasplay fault zone in the Nankai subduction zone under dry and wet conditions. In the dry tests, dehydration of clay minerals occurred by frictional heating, and slip weakening is related to thermal pressurization associated with water vaporization, resulting in a random distribution of clay-clast aggregates in the gouge matrix. In the wet tests, slip weakening is caused by pore-fluid pressurization via shear-enhanced compaction and frictional heating, and there is a very weak dependence of the steady-state shear stress on the normal stress. The resulting microstructure reflects the grain size segregation in a granular-fluid shear flow at high shear rates. These results suggest that earthquake rupture propagates easily through clay-rich fault gouge by high-velocity weakening, potentially leaving the microstructures resulting from the frictional heating or the flow sorting at high slip rates.