The evolution of fault strength and behavior during the initial stages of slip plays an important role in driving the onset of instability and fault weakening. Using small-displacement triaxial experiments on quartz sandstone, this study highlights the rapid onset of microstructural change on fault interfaces and identifies new evidence for an evolution in physical processes with increasing slip and velocity. Pre-ground fault surfaces have been slipped over a range of velocities (0.36 µm s–1 to 18 cm s–1) and at normal stresses comparable to upper- to mid-crustal conditions (92–287 MPa). Microstructural analysis of the fault interfaces reveals the formation of amorphous material at displacements <170 µm and slip durations < 1 ms. Mechanical and microstructural observations have been combined with numerical modeling to present the first documented examples of a transition from mechanical amorphization to flash heating, then frictional melting, with changes in slip conditions. The sequence of processes activated during the initial stages of fault movement may provide new insights into factors that influence the onset of slip in the seismogenic crust.