Lignocellulose fractionation to chemicals and biofuels often requires severe conditions and consume high energy. Although some of these pretreatment processes are nowadays developed at pilot scale, they are not always cost effective, and they are responsible for environmental impacts. Recently, mechanocatalysis pretreatment emerged as a promising technology for the activation and deconstruction of lignocellulosic biomass. In particular, these dry processes have the potential to limit the use of solvent and the production of liquid effluents. In this study, we propose an innovative one-pot eco-friendly approach based on the combination of dry chemical and vibro-ball-milling (VBM) for biomass activation, coupled to enzymatic conversion without an external source of heating, and without the assistance of any organic solvent. NaOH activation coupling to VBM fractionation for 10, 30, and 60 min was compared to H3PO4, H2O2, betaine, and betaine-Cl activation. NaOH-VBM-10 min appears more effective in sugar production compared to other chemical-mechanical activation. NaOH-VBM in 10 min consumed less energy, resulting in higher energy efficiency compared to that of other chemical-mechanical activation. Therefore, NaOH-VBM-10 min appears the most suitable and interesting pretreatment for the production of sugars and biofuels from corn stover biomass.