Flexible metal–organic frameworks, also known as soft porous crystals, have been proposed for a vast number of technological applications, because they respond by large changes in structure and properties to small external stimuli, such as adsorption of guest molecules and changes in temperature or pressure. While this behavior is highly desirable in applications such as sensing and actuation, their extreme flexibility can also be synonymous with decreased stability. In particular, their performance in industrial environments is limited by a lack of stability at elevated temperatures and in the presence of water. Here, we use first-principles molecular dynamics to study the hydrothermal breakdown of soft porous crystals. Focusing on the material MIL-53(Ga), we show that the weak point of the structure is the bond between the metal center and the organic linker and elucidate the mechanism by which water lowers the activation free energy for the breakdown. This allows us to propose strategies for the synthesis of MOFs with increased heat and water stability.