This paper focuses on a novel feedback linearization control (FLC) law based on a self-learning disturbance observer (SLDO) to counteract mismatched uncertainties. The FLC based on BNDO (FLC-BNDO) demonstrates robust control performance only against mismatched time-invariant uncertainties while the FLC based on SLDO (FLC-SLDO) demonstrates robust control performance against mismatched time-invariant and -varying uncertainties, and both of them maintain the nominal control performance in the absence of mismatched uncertainties. In the estimation scheme for the SLDO, the BNDO is used to provide a conventional estimation law, which is used as the learning error for the type-2 neuro-fuzzy system (T2NFS), and T2NFS learns mismatched uncertainties. Thus, the T2NFS takes the overall control of the estimation signal entirely in a very short time and gives unbiased estimation results for the disturbance. A novel learning algorithm established on sliding mode control theory is derived for an interval type-2 fuzzy logic system. The stability of the overall system is proven for a second-order nonlinear system with mismatched uncertainties. The simulation results show that the FLC-SLDO demonstrates better control performance than the traditional FLC, FLC with an integral action (FLC-I), and FLC-BNDO.