In this paper, the influence of miscut-angle on the processing of β-Ga2O3 (100) plane substrates was studied. The morphology changes of (100) plane substrates during the processing were analyzed when the miscut-angles were 0°, 1° and 6°, respectively. Furthermore, the influence of different parameters on the polishing of the substrate was analyzed. The experimental results show that with the increase of the miscut-angle, the cleavage damage of (100) plane substrate reduces, the surface roughness reduces after machining, and the way of material removal transformed from brittle removal to brittle plastic mixed removal to plastic removal. Low polishing pressure can effectively suppress the cleavage damage and improve the surface quality. When the miscut-angle is 6°, the polishing efficiency of (100) plane substrate is high, and the surface roughness after polishing can reach Ra≤0.2 nm.