Different cupric oxide (CuO) structures have attracted intensive interest because of their promising applications in various fields. In this study, three kinds of CuO structures, namely, CuO microdisks, CuO nanoblocks, and CuO microspheres, are synthesized by solution-based synthetic methods. The morphologies and crystal structures of these CuO structures are characterized by field-emission scanning electron microscope and X-ray diffractometer, respectively. They are used as thermal conductive fillers to prepare silicone-based thermal greases, giving rise to great enhancement in thermal conductivity. Compared with pure silicone base, the thermal conductivities of thermal greases with CuO microdisks, CuO nanoblocks, and CuO microspheres are 0.283, 0256, and 0.239 W/mK, respectively, at filler loading of 9 vol.%, which increases 139%, 116%, and 99%, respectively. These thermal greases present a slight descendent tendency in thermal conductivity at elevated temperatures. These experimental data are compared with Nan's model prediction, indicating that the shape factor has a great influence on thermal conductivity improvement of thermal greases with different CuO structures. Meanwhile, due to large aspect ratio of CuO microdisks, they can form thermal networks more effectively than the other two structures, resulting in higher thermal conductivity enhancement.