A two-stage alkaline-oxidative pretreatment of hybrid poplar was investigated at scale (20 L reactor volume) with the goal of understanding how reaction conditions as well as interstage mechanical refining impact downstream process responses. The pretreatment comprises a first stage of alkaline delignification (alkaline pre-extraction) followed by a second delignification stage employing Cu-catalyzed alkaline hydrogen peroxide with supplemental O2 (O2-enhanced Cu-AHP). Increasing pre-extraction severity (i.e., temperature and alkali loading) and pretreatment oxidation (increasing H2O2 loading) were found to increase mass and lignin solubilization in each stage. Lignin recovered from the first stage was subjected to oxidative depolymerization and led to aromatic monomer yields as high as 23.0% by mass. Lignins recovered from the second-stage Cu-AHP pretreatment liquors were shown to exhibit aliphatic hydroxyl contents more than 6-fold higher than a typical hardwood kraft lignin, indicating that these lignins could serve as a biobased polyol for a range of polyurethane applications.