In this work, a nonlinear estimator-based robust controller is designed for the position and yaw control of a quadrotor with uncertainty estimation. This controller ensures the tracking of desired references in the presence of parameters variation and external disturbances, making use of high-order sliding mode (HOSM) estimators to estimate these perturbations that can be canceled by the control, thus improving the dynamic behavior of the controlled system. Its performance is evaluated making use of a Simcenter Amesim quadrotor based on physical models generated from experimental data in a co-simulation framework with Matlab–Simulink used to implement the designed controller with FPGA implementation. A challenging and generic maneuver with time-varying wind disturbances and uncertainty model parameters is considered.