It is laborious and difficult to tune control gains in m-input m-output (MIMO) nonlinear systems using traditional decoupling algorithms, and the overall control performance is not good, so a self-decoupling control (SDC) method was proposed. The method utilized a linear extended state observer (LESO) to estimate and compensate the coupled part, nonlinear part, and disturbance part of the system, and an appropriate control law was designed for self-decoupling the MIMO system. The control gains to be tuned were converted into a parameter, and the convergence of the SDC method was verified by the Lyapunov method. Simulation results of two examples show that the proposed method not only greatly reduced the parameters of the MIMO system to be tuned, but also achieved better control effects than the common active disturbance rejection decoupling control method.