Zn-substituted CaCu3Ti4O12 ceramics were synthesized by solid-state sintering. Their microstructures and dielectric properties were investigated. Ca(Cu1−xZnx)3Ti4O12 single-phase structures were obtained up to x=0.1, and the Cu+/Cu2+ and Ti3+/Ti4+ mixed-valent structure was enhanced with increasing Zn substitution. The giant dielectric response was significantly enhanced by Zn substitution. The dielectric constant increased with increasing x, and a giant dielectric constant plateau as high as ∼9 × 104 was achieved for x=0.1 at 10 kHz, while that for x=0 was ∼3 × 104. The enhanced giant dielectric response was profoundly concerned with the modified mixed-valent structure.