After the October Revolution, the Donskoy Monastery was closed. In 1922–1925, Patriarch Tikhon was detained in this cloister after his arrest. He chose to remain in this monastery after his release. Saint Tikhon's relics were discovered following his canonization in 1989. They are exhibited for veneration in the Great Cathedral in summer and in the Old Cathedral in winter.
In 1924, some of the facilities of the Donskoy Monastery were occupied by a penal colony for children. In 1934, the Donskoy Monastery was transferred under the care of the Museum of Architecture of the Soviet Academy of Architecture. In 1964, the cloister became an affiliate of the Shchusev's Museum of Architecture.
The Soviets moved the remnants of many demolished monasteries and cathedrals to the Donskoy Monastery, including the Cathedral of Christ the Savior, Church of Saint Nicholas the Wonderworker in Stolpy, Church of the Assumption on Pokrovka Street in Moscow, Sukharev Tower, and others.