Practical, economical, and high-selectivity methods of lignin bio-oil upgrading could greatly increase biorefinery productivity and profitability. Herein, we report the efficient production of oxygen-containing fuel via supercritical methanol hydrodeoxygenation (SCM-HDO) of lignin bio-oil with a well-defined Cu/CuZnAlO_x catalyst. The fuel range cyclic alcohols were majorly produced from guaiacol and corncob lignin pyrolysis bio-oil with selectivity of 66.67 and 15.90% at 300 °C in 8 h, respectively, via Cu species induced hydrogenation of aromatics rings and inhibited over-deoxygenation of alcoholic hydroxyl groups. The catalyst activity decreased by 28% after five runs of bio-oil HDO due to the oxidation of Cu species and carbon deposit, where the oxidation of Cu species played the dominant role as the carbon deposit was restrained to as low as 3.64 wt% with the mild catalyst acidity. Meanwhile, the catalyst activity could be easily recovered through a calcination-reduction process to remove the carbon deposit and reactivate the Cu species. The results offered appealing opportunities for tailoring more efficient approaches for the upgrading of lignin bio-oil to alternative biofuels.