Lignin valorisation into chemicals and fuels is of great importance in addressing energy challenges and advancing biorefining in a sustainable manner. In this study, on the basis of the high microwave absorption performance of carbon nanotubes (CNTs), a series of copper-oxide-loaded CNT catalysts (CuO/CNT) were developed to facilitate the oxidative depolymerization of lignin under microwave heating. This catalyst can promote the activation of hydrogen peroxide and air, effectively generating a range of reactive oxygen species (ROS). Through the application of electron paramagnetic resonance techniques, these ROS generated under different oxidation conditions were detected to elucidate the oxidation mechanism. The results demonstrate that the •OH and O2•− play a crucial role in the formation of aldehyde and ketone products through the cleavage of lignin Cβ-O and Cα-Cβ bonds. We further evaluated the catalytic performance of the CuO/CNT catalysts with three typical lignin feedstocks to determine their applicability for lignin biorefinery. The bio-enzymatic lignin produced a 13.9% monophenol yield at 200 °C for 20 min under microwave heating, which was higher than the 7% yield via hydrothermal heating conversion. The selectivity of G-/H-/S-type products was slightly affected, while lignin substrate had a noticeable effect on the selective production. Overall, this study explored the structural characteristics of CuO/CNT catalysts and their implications for lignin conversion and offered an efficient oxidation approach that holds promise for sustainable biorefining practices.