Rock materials show dramatic dynamic weakening in large-displacement (m), high-velocity (∼1 m/s) friction experiments, providing a mechanism for the generation of large, natural earthquakes. However, whether such weakening occurs during induced M3-4 earthquakes (dm displacements) is unknown. We performed rotary-shear experiments on simulated fault gouges prepared from the source-, reservoir- and caprock formations present in the seismogenic Groningen gas field (Netherlands). Water-saturated gouges were subjected to a slip pulse reaching a peak circumferential velocity of 1.2–1.7 m/s and total displacements of 13–20 cm, at 2.5–20 MPa normal stress. The results show 22%–81% dynamic weakening within 5–12 cm of slip, depending on normal stress and gouge composition. At 20 MPa normal stress, dynamic weakening from peak friction coefficients of 0.4–0.9 to 0.19–0.27 was observed, probably through thermal pressurization. We infer that similar effects play a key role during induced seismic slip on faults in the Groningen and other reservoir systems.