Herein, the hydrothermal stability of amorphous silica–alumina (ASA) is investigated under conditions relevant for the catalytic conversion of biomass, namely in liquid water at 200 °C. The hydrothermal stability of ASA is much higher than that of pure silica or alumina. Interestingly, the synthetic procedure used plays a major role in its resultant stability: ASA prepared by cogelation (CG) lost its microporous structure, owing to hydrolysis of the siloxane bonds, but the resulting mesoporous material still had a considerable surface area. ASA prepared by deposition precipitation (DP) contained a silicon-rich core and an aluminum-rich shell. In hot liquid water, the latter structure was transformed into a layer of amorphous boehmite, which protected the particle from further hydrolysis. The surface area showed relatively minor changes during the transformation. Independent of the synthetic method used, the ASAs retained a considerable concentration of acid sites. The concentration of acid sites qualitatively followed the changes in surface area, but the changes were less pronounced. The performance of different ASAs for the hydrolysis of cellobiose into glucose is compared.