The building, constructed between 1915 and 1917 based on the design by architect A.N. Sokolov, was created in collaboration with the renowned experimental physicist P.N. Lebedev, the founder of the first scientific physics school in Russia. Although Lebedev did not live to see the completion of the construction, his consultations during the planning stage helped Sokolov create a building perfectly suited for scientific experiments.

The need for the construction of the Physical Institute arose after the events of 1911 at Moscow University. At that time, about a hundred professors and associate professors, including V.I. Vernadsky, S.A. Chaplygin, A.A. Eikhenvald, G.I. Rossolimo, K.A. Timiryazev, and P.N. Lebedev, left the university in protest against the actions of the Minister of Education L.A. Kasso, who imposed police functions on the university administration. Their departure from the university deprived them of the opportunity to conduct scientific experiments, as the university was practically the only place in Moscow for such research.

The scientists and teachers who resigned founded the Society of the Moscow Scientific Institute, which became the basis for the Physical Institute. In January 1917, it opened in a new building on Miusskaya Square. After nationalization in 1917, the Institute of Biological Physics was located here under the leadership of Academician P.P. Lazarev. On April 22, 1922, on the eve of the operation to extract the bullets remaining from the assassination attempt on Fanny Kaplan, V.I. Lenin was brought here for an X-ray examination. A bullet in the neck area was easily palpable and could be removed without complications, while another bullet in the left shoulder did not interfere and did not require removal.

After the X-rays, Lenin went with Academician Lazarev to inspect the institute, but the inspection was unsuccessful as Lenin became interested in the materials on the Kursk magnetic anomaly and asked the academician to familiarize him with them in detail.

In 1931, Academician Lazarev, who lived in the Institute building, was arrested on political charges. On April 25, 1934, the Council of People's Commissars decided to relocate the Academy of Sciences of the USSR from Leningrad to Moscow. The only building at that time housed the Physical Institute of the Academy of Sciences of the USSR (FIAN), which was headed by the future President of the Academy of Sciences of the USSR S.I. Vavilov.

Currently, the building is owned by the Russian Federation and is managed by the Federal State Institution "Federal Research Center Institute of Applied Mathematics named after M.V. Keldysh of the Russian Academy of Sciences." The completion of restoration work aimed at strengthening the foundation and load-bearing walls is scheduled for 2019.