Direct and efficient conversion of abundant renewable biomass carbohydrates to 5-ethoxymethylfurfural (EMF), a potential biofuel candidate, is highly desirable but remains challenging. We report here the catalytic transformation of glucose using hybrid Hβ and USY zeolites in 1,4-dioxane-contained ethanol solution, leading to EMF production with an excellent yield of 60% within 1h. Hybrid zeolites rational modulate the chemical space, acidity, and acid sites synergistically to drive the imperative cascade reactions during the conversion. Equally important, the introduction of low-polarity aprotic 1,4-dioxane co-solvent can effectively stabilize the obtained EMF because the preferential solubilization of EMF by 1,4-dioxane resulted in a reduction of their nucleophilic charge, which in turn lowers its susceptibility to nucleophilic attack and minimizes the undesirable reactions. This work not only develops a promising protocol for EMF production from glucose but also sheds light on the mechanistic role of hybrid zeolites and 1,4-dioxane co-solvent in the cascade transformation.