As a function of material-specific properties a multiple substrate treatment (MST) for preparation of (0 0 1) ZnSe surfaces for homoepitaxy was developed including cutting, mechanical processing, chemo-mechanical polishing procedure and a final step of chemical polishing. The resulting average roughness of the treated surfaces investigated by atomic force microscopy is less than 1 nm when MST is completed. High-resolution X-ray diffraction topography has been carried out to detect the underlying structural degradation caused by mechanical and chemo-mechanical polishing. The thickness of the damaged layer determined by high-resolution X-ray diffraction rocking curve measurements using 311 reflection (penetration depth ≈800 nm) is about 10 μm and can be removed by means of a final chemical polishing step.