The effects of vibration amplitude on the interface reaction and mechanical strength of the Cu/Al joints were systematically investigated in ultrasonic spot welding (USW) experiments. The appropriate vibration amplitude (22.5 μm) was beneficial for obtaining a sound joint. The formation of the continuous intermetallic compounds (IMC) layer accelerated with a higher vibration amplitude. The lap shear tensile strength of the Cu/Al joints decreased when the thickness of the intermetallic layer was greater than 1 μm at various amplitudes. With the increase in welding time, a crack occurred in the copper side owing to the occurrence of the eutectic reaction, $\mathit{\alpha -A}l+\theta \to L$ , at the periphery of the nugget. The remarkable decline of ultrasonic power curves occurred at various amplitude levels upon the formation of a crack in the copper side.