Rhyolite-hosted hydrothermal systems in the continental crust contain valuable energy and mineral resources that make them of special interest across several scientific disciplines. Despite extensive research on these systems, the temperature-dependence of chemical reactions between host rocks and aqueous-rich fluids and the mineralogical transformations resulting from these reactions are not well quantified. To expand our understanding of the controlling processes operating in these systems, we carried out seven laboratory experiments in which rhyolite was reacted with deionized water at 150 °C to 350 °C and 25 MPa. An additional experiment at 200 °C was carried out to examine the effect of dissolved CO 2 on the reactions. The overarching goal of this experimental study was to provide new insights on the temperature-dependence of water-rock interaction in continental hydrothermal systems. We applied a wide range of chemical, isotopic and mineralogical methods to analyze the reacted rhyolite and waters, and the major observations are: (1) the rhyolite progressively hydrates with increasing temperature between 150 °C to a maximum of 8.2 wt% H 2 O at 275 °C; hydration then decreases until 350 °C in conjunction with the destruction of the rhyolite glass and crystallization of secondary mineral phases; (2) the ratio of molecular water (H 2 O m ) to hydroxyl (OH − ) of the water that is dissolved in the reacted rhyolite decreases from ∼7 at 150 °C to ∼4 at 250 °C; (3) the main secondary minerals formed are the zeolite ferrierite (T ≥ 275 °C); biotite, albite and cristobalite mainly form at higher experimental temperatures (T ≥ 300 °C); (4) the reacted waters are nearly saturated with respect to amorphous silica; (5) at temperatures ≥ 275 °C nearly all the chlorine is leached into solution; (6) fluorine leaching from the rhyolite gradually increases between 150 °C and 250 °C, but then gradually decreases at higher temperatures and is incorporated into a secondary mineral phase; (7) dissolved CO 2 in the water enhances alkali metal cation leaching from the rhyolite; and (8) calculated Na-K and silica geothermometer temperatures differ from the experimental temperatures by varying amounts. In addition, apart from some small lithium isotope fractionation at temperatures ≤ 250 °C, the stable isotopes of boron, lithium and chlorine do not fractionate during rhyolite-water reactions, and the stable isotope compositions of these species in the reacted water are similar to those in the reactant rhyolite. These results provide new insights for a broad range of applications, including quantifying processes involving rhyolite glass hydration (obsidian hydration dating, perlite formation and discriminating secondary from magmatic water in rhyolitic matrix-glass of volcanic pyroclasts), for geothermal energy and mineral deposit exploration and for monitoring volcanoes.