Abstract Using the context of trajectory estimation and tracking for multi-rotor UAVs, we explore the challenges in applying high-gain observers to highly dynamic systems. The multi- rotor will operate in the presence of external disturbances and modeling errors. At the same time, the reference trajectory is unknown and generated from a reference system with unknown or partially known dynamics. We assume the only measurements that are available are the position and orientation of the multi-rotor and the position of the reference sys- tem. We adopt an extended high-gain observer (EHGO) estimation framework to estimate the unmeasured multi-rotor states, modeling errors, external disturbances, and the reference trajectory. We design a robust output feedback con- troller for trajectory tracking that comprises a feedback linearizing controller and the EHGO. The proposed control method is rigorously analyzed to establish its stability properties. Finally, we illustrate our theoretical results through numerical simulation and experimental validation in which a multi-rotor tracks a moving ground vehicle with an unknown trajectory and dynamics and successfully lands on the vehicle while in motion.