This paper presents the design and development of a new flexure-based XYZ micropositioner with a hybrid kinematic configuration. A piezoelectric-driven Z stage is embedded into a parallel-kinematic XY stage actuated by two voice coil motors. The XYZ micropositioner features a sizeable workspace with a compact architecture, which benefits from employing deployable mechanisms and mixed actuators. One uniqueness is that the Z-axis crosstalk error of the XYZ micropositioner is compensated by the closed-loop motion control of the Z stage, which achieves a constant vertical position of the center platform when performing planar motion tasks. Analytical models have been derived based on fixed-guided beam theory to assess the driving stiffness of the mechanism. The finite element analysis is carried out to verify the accuracy of the derived models. A prototype system of the XYZ micropositioner is fabricated with the dimension of 116 mm × 116 mm × 45 mm (i.e., 216 mm × 216 mm × 45 mm with actuators). Experimental results indicate that it obtains a workspace of 4.15 mm × 4.06 mm × 0.04 mm with a crosstalk of less than 1% among the three axes. With the active control of the Z-axis position, the vertical crosstalk error has been dramatically reduced from 7.333 to 1.719 µm. The proposed design provides a promising approach to enable pure planar motion for ultrahigh precision applications requiring optical or electron focusing, such as electron beam lithography.