The poor mobility and complex target motion estimation are the two main challenges in the anti-ship attack missions of high-speed guided missiles. In this study, a new wake-homing scheme of supercavitating vehicles is proposed using the gradient wake flow phenomenon. The basic principle of the wake-homing with laser detection and the information which can be obtained are studied. According to the idiosyncrasy of laser detection, the geometrical characteristics of the vessel wake, and the bubble distribution characteristics, the three-dimensional model of bubble density gradient in horizontal plane of the maneuvering target ship wake flow is first built; the guidance law based on the gradient wake flow is designed and tested. Then, simulation results show the validity of the model wake, the guidance law based on the wake gradient information can accurately track the target. From the simulation results, we also can see that the new wake-homing scheme effectively improve the hit probability, reduce the range of loss, reduce power consumption and gentle guidance trajectory, greatly reduce the mobility requirements of the supercavitating vehicles.