Adaptive super-twisting sliding mode observer and controller are proposed for velocity and attitude control of fixed-wing unmanned aerial vehicle (UAV) which has been challenged by the presence of uncertainty and external disturbance. Firstly, the velocity model and quaternion-based attitude error model of fixed-wing unmanned aerial vehicle were established. Then the adaptive super-twisting sliding mode disturbance observer was designed to approximate system disturbance and uncertainty. On this basis, a super-twisting sliding control scheme was proposed to track desired commands of velocity and attitude of UVA. Finally, the stability of the system was proven by Lyapunov theory. The simulation results verified that the integrated control scheme made the UVA track desired commands fast and accurate, and had the excellent robust adaptive ability. The control strategy could also be used to quickly and steadily achieve the expected goal of unmanned aerial vehicles for different flight commands.