Clathrate hydrates (CHs) are ubiquitous in earth under high-pressure conditions, but their existence in the interstellar medium (ISM) remains unknown. Here, we report experimental observations of the formation of methane and carbon dioxide hydrates in an environment analogous to ISM. Thermal treatment of solid methane and carbon dioxide–water mixture in ultrahigh vacuum of the order of 10 −10 mbar for extended periods led to the formation of CHs at 30 and 10 K, respectively. High molecular mobility and H bonding play important roles in the entrapment of gases in the in situ formed 5 12 CH cages. This finding implies that CHs can exist in extreme low-pressure environments present in the ISM. These hydrates in ISM, subjected to various chemical processes, may act as sources for relevant prebiotic molecules. © 2019 National Academy of Sciences. All Rights Reserved.