An earthquake occurs when a fault weakens during the early portion of its slip at a faster rate than the release of tectonic stress driving the fault motion. This slip weakening occurs over a critical distance, D(c). Understanding the controls on D(c) in nature is severely limited, however, because the physical mechanism of weakening is unconstrained. Conventional friction experiments, typically conducted at slow slip rates and small displacements, have obtained D(c) values that are orders of magnitude lower than values estimated from modelling seismological data for natural earthquakes. Here we present data on fluid transport properties of slip zone rocks and on the slip zone width in the centre of the Median Tectonic Line fault zone, Japan. We show that the discrepancy between laboratory and seismological results can be resolved if thermal pressurization of the pore fluid is the slip-weakening mechanism. Our analysis indicates that a planar fault segment with an impermeable and narrow slip zone will become very unstable during slip and is likely to be the site of a seismic asperity.