An integral sliding mode control method based on fixed time disturbance observer was designed for a 4-DOF underwater vehicle-manipulator system with a 2DOF manipulator. Based on the fixed time characteristics, a fixed time disturbance observer was designed to observe the unmodeled dynamics and external disturbances, and a fixed time trajectory tracking control strategy based on integral sliding mode was designed. The simulation results show that the designed control method can make the end effector of the underwater robot manipulator system track the desired trajectory accurately in a fixed time, and the convergence time is independent of the initial state. This study provides an effective solution to the trajectory tracking control problem of the end effector for the underwater robot manipulator system with unmodeled dynamics and external disturbances.