Aiming at three-dimensional (3D) terminal guidance problem, a novel guidance model is established in this paper, in which line-of-sight (LOS) range is treated as an independent variable, describing the relative motion between the vehicle and the target. The guidance model includes two differential equations that describe LOS’s pitch and yaw motions in which the pitch motion is separately decoupled. This model avoids the inaccuracy of simplified two-dimensional (2D) guidance model and the complexity of 3D coupled guidance model, which not only maintains the accuracy but also simplifies the guidance law design. The application of this guidance model is studied for optimal re-entry guidance law with impact angle constraint, which is presented in the form of normal overload. Compared with optimal guidance laws based on traditional guidance model, the proposed one based on novel guidance model is implemented with the LOS range instead of time-to-go, which avoids the problem of the time-to-go estimation of traditional optimal guidance laws. Finally, the correctness and validity of the guidance model and guidance law are verified by numerical simulation. The guidance model and guidance law proposed in this paper provide a new way for the design of terminal guidance.