Extensive research was undertaken over the past 20 years to investigate the suitability of cadmium zinc telluride (CZT) crystals as a material for room-temperature nuclear-radiation detectors. Large-volume CZT crystals, with thicknesses up to 2 cm and large effective areas of roughly 5–10 cm2, are needed to fabricate efficient detectors that meet the working requirements of federal agencies, such as the DOE/NNSA (Department Energy National Nuclear Security Administration), Department of Homeland Security (DHS), and the Department of Defense (DOD). However, because of the imperfect methods for growing crystals, the resulting large-volume crystals most often are not perfect single ones, and contain structural defects such as voids, pipes, impurities from source materials, tellurium inclusions and precipitates, vacancies, and vacancy-impurity complexes generated during the process of their production. Other extended defects that may be present include grain boundaries, micro twins, and walls of dislocations (sub-grain boundaries). Identifying these defects, controlling their occurrence and eliminating them from the bulk CZT material currently are important tasks that will improve the yield of detector-grade crystals from ingots, and ultimately better their performance. In this study, we used a post-growth thermal annealing technique to remove the performance-limiting defects caused by tellurium inclusions and associated impurities in the CZT crystals. We realized a 66% ± 16% reduction in the size of the inclusions, with an overall elimination of 17% ± 2% of them. We believe that our experimental results offer a better understanding of the optimal annealing parameters, and of the dynamic properties of post-growth annealing processes.