A hybrid-type three-dimensional visual alignment system is suggested, which is to align pattern mask and glass panel for manufacturing flat panel displays. In order to compensate for the spatial misalignments between mask and panel, a pair of decoupled positioning mechanisms are adopted, where the lower 4-PPR parallel kinematic machine provides 3-degree-of-freedom motions to the pattern mask like the current in-plane alignment systems, while the upper 4-RPS machine gives an independent 3-degree-of-freedom mobility to the glass panel along the directions excluded in the mask movement. Hence, the combinatorial motion of the two positioning mechanisms completes a spatial mask–panel alignment. In this article, two fundamental issues are solved for the operation of the hybrid alignment system. First, the inverse kinematic solutions for the hybrid parallel mechanisms are derived to determine the displacements of active joints for an arbitrary misalignment in the task space. Second, it is developed how to extract the spatial misalignment between mask and panel in real time in terms of three in-plane cameras and the focus value Gaussian model.