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Abstract The constitutive behavior of faults intervenes in virtually every aspect of the seismic phenomenon but is poorly understood, particularly regarding how effective normal stress affects the boundaries of the seismogenic zone. Here, we explore the mechanical properties of Pelona schist, Westerly granite, phyllosilicate‐rich gouge, gabbro, hornblende, lawsonite blueschist, montmorillonite, and smectite in hydrothermal conditions at various confining pressures and explain the laboratory observations with a physical model of fault friction. The thermobaric activation of healing and deformation mechanisms explains the boundaries of unstable slip as a function of slip‐rate, temperature, and effective normal stress for a given lithology. The constitutive law affords extrapolation of laboratory data in the conditions relevant to seismic cycles throughout the crust, explaining the focus of large earthquakes in collision, subduction, and continental and oceanic transform settings.