This paper presents an adaptive uncertainty estimator-based proportional-integral (PI) type sliding mode control for a spherical robot with structural uncertainties and external disturbance. By projection method, the 3D robot dynamic model with structural asymmetry is decoupled into the balance subsystem and velocity subsystem, and the kinetics equations are established based on Newton–Euler's law. To estimate the unknown structural dynamics in the balance subsystem and external disturbance in the velocity subsystem, adaptive law containing both control and estimation error information is proposed for the uncertainty estimator (UE) design. Then, an uncertainty estimator-based PI type uncertainty estimator sliding mode controller (UESMC) is introduced for balance and velocity control, leading to enhanced disturbance rejection capability and a reduced steady-state error. Simulations and experiments on a real spherical robot are conducted to demonstrate the efficacy of the proposed control strategies.