Establishing 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 Melange in the Shimanto accretionary complex in Japan. The constitutive model consistently explains the evolving frictional response of fault gouge from room temperature to 600 & DEG;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. The frictional behavior of rocks is essential to understand fault activity and seismic unrest. Despite decades of research, the frictional behavior of rocks remains elusive. Although empirical parameters can be used to characterize the frictional behavior of fault gouge, they cannot consistently capture the evolution of frictional properties with temperature and sliding velocity. This is a theoretical bottleneck to earthquake forecasting. In this article, we present a physical model that explains the complex frictional response of various types of rocks from room temperature to 600 & DEG;C within five orders of magnitude of sliding velocities. The model captures the dominance of distinct healing mechanisms at different ranges of temperature and the transition to crystal plasticity in the fault zone at elevated temperatures. As a result, a single set of constitutive parameters can explain the frictional response of rocks throughout the seismic cycle from the Earth's surface to the bottom of the lithosphere. Frictional properties evolve with the thermal activation of competing healing and deformation mechanisms at different slip-ratesA constitutive law explains gouge friction from room temperature to 600 & DEG;C and slip-rates from nanometers to millimeters per secondThe frictional response during seismic cycles is controlled by lithology and the prevailing hydrothermal conditions