This paper focuses on adaptive integral sliding mode control for a class of underactuated autonomous underwater vehicles (AUVs) with uncertain dynamics, where the vehicles moving in three-dimensional (3-D) space have only three available control inputs provided by the stern propellers, steering and diving rudders but five degrees of freedom to be controlled. Different from the traditional sliding mode control, the proposed dual closed-loop integral sliding mode control design can be described as comprising two distinct phases: 1) in outer-loop, the virtual velocity commands are determined for the following work; 2) in inner-loop, the actual control inputs are designed to achieve the trajectory tracking. Moreover, the practical situations that there exist systematic parametric uncertainties and external disturbances are also considered, and a novel direct adaptive neural network controller combined with a conditional integrator is presented, which provides the robustness and adaptation for the vehicle. In addition, the rigorous stability analysis based Lyapunov’s method demonstrates the uniform ultimate boundedness of all the tracking errors in the closed-loop system. Finally, simulation results are shown the effectiveness of the proposed controllers.