The collection of the Art Museum began to form in 1895 as part of the historical and archaeological museum of the Simbirsk provincial scientific archival commission. After the 1917 revolution, the museum acquired nationalized collections from Simbirsk nobles, industrialists, and merchants, such as V. N. Polivanov, E. M. Persy-French, A. V. Zhirkovich, V. P. Meshcherinov, and N. Ya. Shatrov.

In 1920, the museum became an independent institution and was initially located in the former house of landowner Persy-French. In 1932, it was moved to the Goncharov Memorial House, where it occupied the second floor, while the Ulyanovsk Regional Local History Museum named after I.A. Goncharov was located on the first floor.

In the 1920s and 1930s, the museum was actively replenished with exhibits from the State Museum Fund, the Pushkin House of the Academy of Sciences, and the State Hermitage. Currently, the museum's collections number about 11,607 items.

The museum's collection features unique works of Russian and Western European painting, sculpture, and graphics from the 16th to the 20th centuries. Among the masterpieces of Western European art that define the uniqueness of the collection are works by outstanding masters from France, Spain, and the Netherlands of the 16th-17th centuries, such as N. de Largillière, J. V. Scorrel, H. de Valdes Leal, K. Keynink, and D. Tenirs.

The pride of the museum includes paintings by D. Levitsky, F. Rokotov, V. Borovikovsky, K. Bryullov, and A. Ivanov. The collection of estate portraits created by serf masters from the Simbirsk province is also unique. The decorative and applied arts department includes ancient ceramics from the 4th-3rd centuries BC, porcelain from Russia, Germany, and France, artistic furniture, as well as Russian and Western European glass. The museum possesses significant monographic collections that allow for a comprehensive representation of the works of K. Bryullov, V. Khudyakov, and Ulyanovsk artists such as A. Plastov and D. Arkhangelsky.