The increasing demand for renewable materials in the world has resulted in sustained efforts to utilize biomass in a better way. Lignin, a natural and abundant polymer in plants, has provided an ongoing challenge for many researchers seeking ways to better utilize this abundant resource. Here, we report a very efficient lignin depolymerization strategy with the assistant of microwave radiation. Copper sulphate (CuSO4) and hydrogen peroxide (H2O2) were used to generate hydroxyl radicals to depolymerize lignin under the irradiation of microwaves. Three different types of lignin, organosolv lignin, kraft lignin, and alkali lignin, were all successfully depolymerized using microwave irradiation at a temperature of 110 °C for 7 min. The use of 1H/13C two-dimensional nuclear magnetic resonance spectroscopy enabled the confirmation of structural changes, comparing before and after depolymerization. Liquid chromatography-mass spectrometry was used to characterize the products. Both monomers and oligomers were detected after depolymerization.