In order to achieve high-precision trajectory tracking of hypersonic vehicles, a trajectory tracking algorithm for highly maneuverable targets combining moving horizon estimation and an interactive multi-model (IMM) algorithm was proposed. Firstly, the motion model and measurement model of the glide segment of the hypersonic vehicle under the half-velocity system were given. Then, the moving horizon estimation method was used to transform the state estimation problem into a constrained optimization problem, and the physical constraints of the glide segment of the flight vehicle were fully considered. On this basis, in order to cope with the different maneuver modes of the target, a model set was established to approximate it with the help of the IMM algorithm. Finally, the algorithm was verified under unchanged and mutated maneuver modes. The results show that the new algorithm adopts parallel estimation of multiple models, and the model probability is adjusted in real time for fusion output, which can effectively avoid the mismatch of the target tracking model and significantly improve the trajectory tracking accuracy of highly maneuverable targets such as hypersonic vehicles.