High-tech facilities engaged in the production of semiconductors and optical microscopes are extremely expensive, which may require time-domain analysis for seismic resistant design in consideration of the most critical directions of seismic ground motions. This paper presents a framework for generating three-dimensional critical seismic ground acceleration time histories compatible with the response spectra specified in seismic design codes. The most critical directions of seismic ground motions associated with the maximum response of a high-tech facility are first identified. A new numerical method is then proposed to derive the power spectrum density functions of ground accelerations which are compatible with the response spectra specified in seismic design codes in critical directions. The ground acceleration time histories for the high-tech facility along the structural axes are generated by applying the spectral representation method to the power spectrum density function matrix and then multiplied by envelope functions to consider nonstationarity of ground motions. The proposed framework is finally applied to a typical three-story high-tech facility, and the numerical results demonstrate the feasibility of the proposed approach.