To solve the problems of external disturbances and the uncertainty of system model parameters for the underactuated quadrotor Unmanned Aerial Vehicle (UAV) existing in actual flight, a flight control scheme based on Extended State Observer (ESO) and integral backstepping sliding mode was designed. Firstly, according to the semi-coupling characteristics and the strict feedback architecture of system, a backstepping control was adopted to design the attitude inner loop and the position outer loop controllers. Then, a sliding mode algorithm with strong anti-jamming ability and integral control were incorporated to enhance system robustness and reduce static error respectively. Finally, ESO was used to eliminate the total internal and external disturbances and to compensate the interference in the control law online. The closed-loop control system was proven to be globally asymptotically stable by the Lyapunov stability analysis. In addition, the effectiveness and robustness of the proposed flight control scheme were verified through simulation analysis.