An adaptive cerebellar-model-articulation-controller (CMAC)-based supervisory control system is developed for uncertain nonlinear systems. This adaptive CMAC-based supervisory control system consists of an adaptive CMAC and a supervisory controller. In the adaptive CMAC, a CMAC is used to mimic an ideal control law and a compensated controller is designed to recover the residual of the approximation error. The supervisory controller is appended to the adaptive CMAC to force the system states within a predefined constraint set. In this design, if the adaptive CMAC can maintain the system states within the constraint set, the supervisory controller will be idle. Otherwise, the supervisory controller starts working to pull the states back to the constraint set. In addition, the adaptive laws of the control system are derived in the sense of Lyapunov function, so that the stability of the system can be guaranteed. Furthermore, to relax the requirement of approximation error bound, an estimation law is derived to estimate the error bound. Finally, the proposed control system is applied to control a robotic manipulator, a chaotic circuit and a linear piezoelectric ceramic motor (LPCM). Simulation and experimental results demonstrate the effectiveness of the proposed control scheme for uncertain nonlinear systems.