The mechanism of the combined process of ion beam sputtering (IBS) and HF acid etching on the chemical structure defects of fused silica and its laser damage resistance performance were investigated in this paper. During the removal process of surface material, the sputtering effect causes lattice atoms to flee their native space locations, and a large amount of unsaturated chemical structures are produced on the silica surface, which improves the chemical activity of Si and O atoms, accelerates the chemical reaction process between surface atoms and water molecules, increases the content of hydroxyl groups (OH-) in the shallow layer, and enhances the photothermal weak absorption intensity. However, the increase in hydroxyl content weakens the binding strength of silicon–oxygen bonds, destroys the spatial network structure of silica bulk, and reduces its mechanical strength, resulting in a decrease in its laser damage resistance performance. The paper reveals for the first time the mechanism by which IBS changes the structure characteristics of silica material, accelerates the surface hydroxylation process, and thereby reduces the laser damage resistance performance. This work provides technical guidance for effectively suppressing chemical structure defects on silica surfaces and improving the laser damage resistance performance of optical components under high-flux laser irradiation.