This work is dedicated to the development of new performing Zr-O-W-mixed oxide catalysts for the direct conversion of fructose to 5-hydroxymethylfurfural (5-HMF) under soft operational conditions. By using sol–gel method, nanoclusters of WOx as active phase could be formed on the surface of the catalyst at low W loading (i.e., atomic ratio of W/Zr = 1/9), as revealed by different physico-chemical characterizations (scanning transmission electron microscope with a high-angle annular dark field [STEM-HAADF], X-ray diffraction [XRD], X-ray photoelectron spectroscopy [XPS], etc.). The prepared catalysts show very good catalytic performance in the direct conversion of fructose into 5-HMF under soft reaction conditions with the highest HMF yield of 95.8% (reaction conditions: 10 g/L catalyst loading, 120°C, 2 h of reaction, 5 wt.% of fructose in dimethyl sulfoxide [DMSO] solvent).