The efficient production of levulinic acid (LA) from biomass fructose was achieved in micropacked bed reactors (μPBRs) over HND-580. Based on the residence time distribution (RTD) experiment, it was determined that the flow behavior of the single liquid phase flow in μPBRs was close to plug flow with the dimensionless axial dispersion number of 0.0083−0.0352. The mean residence time is 31.4−968.3 s under the experimental range; 98.2% fructose conversion and 74.9% LA yield were obtained within 454.2 s at 150 °C, 0.1 mL/min, and 2.0 MPa. Under the same conditions, 100% conversion and 98.3% LA yield were obtained by selecting HMF as substrate. The space-time yield (STY) of LA in μPBRs was 1−2 orders of magnitude larger than that of conventional batch reactors. Also, a kinetic model was established to predict the fructose conversion rate and LA yield, and the fitting degree with the experimental value was 0.978.