Two 2.25-cm3 CdZnTe gamma-ray spectrometers with three-dimensional (3-D) position sensitivity were constructed and tested. By using 11 × 11 pixellated anodes and depth-sensing techniques, individual spectral data for each of ∼4800 voxels were collected throughout the detector volume. Energy resolution of 1.11% and 1.14% FWHM at 662 keV were obtained for single-pixel events from these two detectors, respectively. Spatial variations of electron mobility-lifetime product, energy resolution, photopeak efficiency, and total efficiency have been observed and analyzed. This analysis provides a direct observation on the uniformity of detector response (due to material, weighting potential, and electric field distribution) in 3-D. Possible defects in the detector are identified. The impact of the spatial variation of detector response on a CZT gamma-ray spectrometer is discussed.