Dissociative chemisorption of ethanol on partially dehydroxylated silica is investigated by (i) exposing silica to gas-phase ethanol at various temperatures (ranging between 373 and 773 K) and (ii) analyzing the material using temperature-programmed desorption and in situ infrared spectroscopy. This chemisorption leads to formation of isolated surface ethoxide species via dehydration of ethanol at reaction temperatures above 573 K, and, at lower temperatures, it favors the synthesis of silanol–ethoxide functionality via a pathway involving opening of siloxane Si–O–Si bridges. The activation barrier for ethene desorption from the isolated surface ethoxide species is considerably higher relative to that for ethanol desorption from the hydrogen-bound silanol–ethoxide pairs. These single-turnover experiments allow predicting the product distribution of ethanol chemisorption on silica depending on the treatment conditions, e.g. temperature of interaction between ethanol and silica, and suggest why, in general, dehydration catalysis on silica requires high temperatures, in order to avoid non-productive chemisorption via opening of siloxane bridges.