A lignin-first biorefinery based on oxidative fractionation of lignocellulose is presented for the first time. Red oak was successfully delignified through alkaline oxidation yielding carbohydrate pulp and phenolic monomer-rich lignin oil. Process conditions for optimizing phenolic monomer yield, cellulose retention in the pulp, and delignification were explored. The effect of temperature, oxygen partial pressure, time, catalyst, and sodium hydroxide concentration were assessed using a response surface statistical method. Two different operating windows were proposed to get the optimum results. Temperature and time were the most significant explanatory variables for all the response models. The presence of CuSO4 catalyst was of slight significance in the production of monomers if reaction time was short. Under optimum reaction conditions, the lignin oil consisted of around 40% phenolic monomers (mainly syringaldehyde and vanillin). The structural features of the lignin oil were further analyzed by GC/MS, GPC, and 2D HSQC NMR techniques. The isolated carbohydrate pulp retained approximately 97 wt% of the cellulose under optimum reaction conditions. Powder X-ray diffraction of the isolated carbohydrate pulp showed that the cellulose was of crystalline structure, indicating its potential for paper production. Enzymatic hydrolysis of the carbohydrate pulp converted 85% of the cellulose to glucose within 120 h, illustrating the potential of cellulosic ethanol production via this lignin-first strategy.