One of the biggest challenges for large size three-dimensional (3D) holographic display based on the computer-generated hologram (CGH) is the trade-off between computation time and reconstruction quality, which has limited real-time synthesis of high-quality holographic image. In this paper, we propose a superpixel-based sub-hologram (SBS) method to reduce the computation time without sacrificing the quality of the reconstructed image. The superpixel-based sub-hologram method divides the target scene into a collection of superpixels. The superpixels are composed of adjacent object points. The region of the superpixel-based sub-hologram corresponding to each superpixel is determined by an approximation method. Since the size and the complexity of the diffraction regions are reduced, the hologram generation time is decreased significantly. The computation time has found to be reduced by 94.89% compared with the conventional sub-hologram method. It is shown that the proposed method implemented on the graphics processing unit (GPU) framework can achieve real-time (> 24 fps) color three-dimensional holographic display with a display size of 155.52 mm × 276.48 mm.