The Tretyakov family acquired a house on Lavrushinsky Lane in 1851, although the history of this property dates back to the late 17th century. At that time, stone chambers stood here, which were repeatedly rebuilt, including during the Kologrivovs in the 18th century. From 1835 to 1839, the merchants Shestovy carried out another reconstruction.

In 1856, Pavel Mikhailovich Tretyakov bought the first paintings by Russian artists: "Clash with Finnish Smugglers" by Vasily Khudyakov and "Temptation" by Nikolai Shilder, marking the beginning of his famous collection. Over time, space for the growing collection became insufficient, and in 1872 he added an additional wing for the gallery to the southwest corner of the house. In the 1880s, new buildings were erected according to the project of architect A. S. Kaminsky, including a building on Malaya Tolmachevsky Lane, as well as a fence with a grand entrance from Lavrushinsky Lane.

In 1892, Tretyakov transferred his collection to Moscow, which included 1,287 paintings, 518 drawings, and 9 sculptures by Russian artists of the 18th-19th centuries, as well as 75 paintings by his brother Sergey. Pavel Mikhailovich became the lifetime curator of the gallery. After his death in 1899-1900, the house was rebuilt for the needs of the gallery, and in 1902, the buildings on Lavrushinsky Lane were unified with a new facade designed by V. M. Vasnetsov, creating the familiar appearance of the Tretyakov Gallery.

In 1913, I. E. Grabar became the curator of the gallery, who led it after the revolution. In the 1920s and early 1930s, several neighboring properties were added to the gallery, including the closed Church of St. Nicholas the Wonderworker in Tolmachi. In 1936, an additional two-story building was constructed according to the project of A. V. Shchusev, which soon became part of the main exhibition.

During the Great Patriotic War, the gallery's exhibits were evacuated to Novosibirsk and Perm, and the building suffered from air raids. By 1944, most of the halls had been restored.

In the mid-1980s, the construction of a depository and a new museum building at the corner with Bolshoy Tolmachevsky Lane began, which turned out to be unsuccessful from an architectural point of view. The main building was renovated while preserving its historical appearance, and the work was completed by 1995. The museum complex includes the Church of St. Nicholas the Wonderworker in Tolmachi, which became a house temple-museum, housing the miraculous Vladimir Icon of the Mother of God.

Today, the gallery's collection includes over 170,000 works of art. It is not only one of the renowned world museums but also a major scientific and restoration center.