Several lines of evidence, including remote triggering of earthquakes and modulation of seismic tremor by Earth tides, suggest that faults weaken when subject to shaking and dynamic stresses associated with the passage of seismic waves. However, the origin of such dynamic weakening is poorly understood. Here we explore the role of acoustic resonance for dynamic fault weakening using laboratory measurements. Experiments were conducted using a split Hopkinson pressure bar assembly, with dynamic stressing via impact loading. Samples were composed of crushed rock particles from mine tailings with a particle size distribution similar to that found in a natural fault gouge. We used pulse-shaper techniques and carefully evaluated dynamic stresses recorded at the front and rear of the sample to ensure that dynamic force balance was satisfied. Our experiments document acoustic-induced fluidization and dramatic dynamic weakening. Frictional strength and elastic modulus of a simulated fault gouge are reduced by a factor of 5–10 via acoustic fluidization. We find a threshold acoustic pressure for fluidization that varies systematically with gouge zone properties. Our observations could help explain dynamic fault weakening and triggering of earthquake fault slip by dynamic stressing.