AbstractEstablishing a constitutive law for fault friction is a crucial objective of earthquake science. However, the complex frictional behavior of natural and synthetic gouges in laboratory experiments eludes explanations. Here, we present a constitutive framework that elucidates the rate, state, and temperature dependence of fault friction under the relevant sliding velocities and temperatures of the brittle lithosphere during seismic cycles. The competition between healing mechanisms, such as viscoelastic collapse, pressure‐solution creep, and crack sealing, explains the low‐temperature stability transition from steady‐state velocity‐strengthening to velocity‐weakening as a function of slip‐rate and temperature. In addition, capturing the transition from cataclastic flow to semi‐brittle creep accounts for the stabilization of fault slip at elevated temperatures. We calibrate the model using extensive laboratory data on synthetic albite and granite gouge, and on natural samples from the Alpine Fault and the Mugi Mélange in the Shimanto accretionary complex in Japan. The constitutive model consistently explains the evolving frictional response of fault gouge from room temperature to 600°C for sliding velocities ranging from nanometers to millimeters per second. The frictional response of faults can be uniquely determined by the in situ lithology and the prevailing hydrothermal conditions.