This paper reports the design and development processes of a totally decoupled flexure-based XYZ parallel-kinematics micropositioning stage with piezoelectric actuation. The uniqueness of the proposed XYZ stage lies in that it possesses both input and output decoupling properties with integrated displacement amplifiers. The input decoupling is realized by actuation isolation using double compound parallelogram flexures with large transverse stiffness, and the output decoupling is implemented by employing two-dimensional (2-D) compound parallelogram flexures. By simplifying each flexure hinge as a two-degree-of-freedom (2-DOF) compliant joint, analytical models of kinematics, statics, and dynamics of the XYZ stage are established and then validated with finite-element analysis (FEA). The derived models are further adopted for optimal design of the stage through particle swarm optimization (PSO), and a prototype of XYZ stage is fabricated for performance tests. The nonsymmetric hysteresis behavior of the piezo-stage is identified with the modified Prandtl-Ishlinskii (MPI) model, and a control scheme combining the inverse model-based feedforward with feedback control is constructed to compensate the plant nonlinearity and uncertainty. Experimental results reveal that a submicron accuracy 1-D and 3-D positioning can be achieved by the system, which confirms the effectiveness of the proposed mechanism and controller design as well.