This work investigates the non-synchronous observer-based output feedback control of nonlinear systems by T-S fuzzy affine models. In order to estimate the unmeasurable system states and handle the non-synchronization issue of premise variables between the observer/controller and the original system, a new non-synchronous piecewise fuzzy affine observer is firstly synthesized to estimate the unmeasurable system state variables. Via utilizing some elegant matrix inequalities with convexification techniques, new observer-based piecewise output feedback controller design results are proposed within the framework of piecewise quadratic Lyapunov functions. Simulation studies are given to illustrate the validity of the developed approach.