Abstract: Abstract：Objectives To address the high-performance trajectory tracking control problem for the unmanned underwater vehicle (UUV) under external disturbances, this paper proposes a non-singular integral terminal sliding mode control (NITSMC) scheme based on a nonlinear disturbance observer (NDOB). Methods First, the dynamic equation of UUV with lumped disturbances is established. Then, an NDOB is designed to estimate the lumped disturbances, and based on the disturbances estimation, an NITSMC law is designed. This effectively compensates for the disturbances and achieves fast and precise tracking of the desired trajectory. Finally, the effectiveness and superiority of the designed NDOB-NITSMC control scheme are validated through comparative simulations against the integral sliding mode control (ISMC) and PID control methods. Additionally, the effectiveness and practicality of NDOB-NITSMC are confirmed through water tank experiments. Results In high-fidelity simulations, the NDOB-NITSMC scheme ensures that the positions and yaw angle errors can converge to a small neighborhood around zero within 8 s, with root mean squared errors (RMSEs) of 0.31 cm, 0.22 cm, 0.29 cm, and 0.23° , respectively. The convergent speed and control accuracy surpass those of ISMC and PID control methods. In water tank experiments, NDOB-NITSMC can ensure the positions and yaw angle errors can converge to a small neighborhood around zero within 15 s, with RMSEs of 2.31 cm, 2.56 cm, 2.17 cm, and 1.11°, respectively. Additionally, the control inputs are smooth, ensuring suitability for practical engineering applications. Conclusions The proposed NDOB-NITSMC scheme effectively addresses the high-performance trajectory tracking control problem for UUV under external disturbances and demonstrates promising prospects for engineering applications.