Hemicelluloses are the earth's second most abundant structural polymers, found in lignocellulosic biomass. Efficient enzymatic depolymerization of xylans by cleaving their β-(1 → 4)-glycosidic bonds to produce soluble sugars is instrumental to the cost-effective production of liquid biofuels. Here we show that the multi-scale two-phase process of enzymatic hydrolysis of amorphous hemicelluloses is dominated by its smallest scale-the pores. In the crucial first five hours, two to fourfold swelling of the xylan particles allow the enzymes to enter the pores and undergo rapid non-equilibrium adsorption on the pore surface before they hydrolyze the solid polymers, albeit non-competitively inhibited by the products xylose and xylobiose. Rapid pore-scale reactive dissolution increases the solid carbohydrate's porosity to 80-90%. This tightly coupled experimental and theoretical study quantifies the complex temporal dynamics of the transport and reaction processes coupled across scales and phases to show that this unique pore-scale phenomenon can be exploited to accelerate the depolymerization of hemicelluloses to monomeric sugars in the first 5-6 h. We find that an 'optimal substrate loading' of 5 mg/ml (above which substrate inhibition sets in) accelerates non-equilibrium enzyme adsorption and solid hemicellulose depolymerization at the pore-scale, which contributes three-quarters of the soluble sugars produced for bio-alcohol fermentation.