A short time before the city was liberated by Ukrainian forces, the collection was moved to the Central Museum of Taurida in Simferopol in Russian-occupied Crimea.

[4][5] Archaeologist and public figure Victor Ivanovich Goshkevich founded an archaeological museum in Kherson in 1890.

Additions during this period included paintings by Oleksy P. Bogolyubov, I. F. Kolesnikov, Kirill V. Lemokh, Vladimir E.Makovsky, V. D. Polenova, Mykola K. Pymonenko, S. S. Yegornov, and V. I. Zarubin, and works by sculptors I.

In the period of the 20s and 30s following World War I, the collection museum was replenished with works by Russian and Western European masters.

During the years of fascist occupation, the Nazis took most of the museum's valuables, including a collection of works of art, from Kherson to sites in Germany and Romania.

After the liberation of the city in March 1944, attempts were made to repatriate items from the original collection, but it was not until 1966 with the art department was opened.

Of the four anonymously-submitted proposals presented at the Duma-approved competition, the design by Odessa-born architect Adolf Borisovich Minkus (1870–1948) prevailed.

On October 31, 2022, just prior to the city's liberation by Ukrainian forces, Russian trucks began to line up outside the museum.