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Abstract Among many biomass‐derived intermediate compounds, 5‐hydroxymethylfurfural (HMF) has been regarded as a platform chemical because it can be used to produce numerous valuable products. However, the difficulty of HMF isolation from reaction media coupled with its poor stability have significantly inhibited its large‐scale production and application. In this work, we report a single‐step process for the direct production of HMF from glucose using green chemical methods. Optimized glucose isomerization and dehydration under microwave irradiation achieved a respectable HMF yield (70 %) using a biphasic solvent mixture (water/THF), high glucose concentration (30 % w/v), catalytic amounts of AlCl₃(5 mol%) and HCl (15 mol%). The reaction can be completed within minutes at 165 °C. Overall, our microwave‐assisted strategy enables the direct conversion of commercially available glucose to the highly valuable platform chemical HMF without the use of expensive solvents or catalysts, suggesting an economically attractive approach for upgrading carbohydrates.