Glucose dehydration has been studied over aluminum (AlPO), titanium (TiPO), zirconium (ZrPO), and niobium phosphates (NbPO). The experimental results suggest that the activity of glucose transformation decreases in the order: NbPO > ZrPO > TiPO > AlPO, which was determined to correspond to the amount of strong acid sites on these catalysts. The selectivity to 5-hydroxymethylfurfural (HMF) varies in the range of 30–60% and depends on the ratio of Brönsted to Lewis acid sites. Excess of Lewis acidity on the catalyst leads to unselective glucose transformation into humins. Modification of the catalysts by a silylation procedure or by deeper treatment with phosphoric acid leads to drastic increase in the selectivity to HMF due to the deactivation of unselective Lewis acid sites. It is proposed that a synergism of a protonated phosphate group and a nearby metal Lewis acid site in the two-stage glucose transformation into HMF leads to a highly selective glucose dehydration.