Biomass-derived 2,5-dimethylfuran (DMF) is an ideal, renewable gasoline additive, and its production with high productivity is highly desirable. A continuous production route was developed to yield DMF from fructose via a tandem strategy, where dehydration catalysts (HY zeolite and niobium phosphate) assisted by 1-butyl-3-methylimidazolium chloride ([BMim]Cl) and hydrodeoxygenation (HDO) catalyst Cu−Ru/C were integrated into one reaction system with γ-butyrolactone (GBL) as the mobile phase. Optimum conditions, such as temperature, H 2 pressure, weight hourly space velocity, and [BMim]Cl concentration, were investigated systematically, with an initial HDO study by using 5hydroxymethylfurfural (HMF) as substrate and subsequent tandem dehydration and HDO to produce DMF with fructose as substrate. Among the conditions, the highest yield of DMF at 55.2% was gained by niobium phosphate and Cu−Ru/C, with the aid of [BMim]Cl in a fixed bed. Meanwhile, [BMim]Cl facilitated fructose dehydration to HMF and also mediated HDO of the resultant HMF by stabilization, which was clarified by 1 H NMR and FTIR spectroscopy. Finally, the fact that carbon deposit led to catalyst deactivation was examined thoroughly via a series of characterization techniques. This work achieved continuous DMF production from fructose and laid a foundation for future possible amplification of DMF.