The basis of the museum's collection was the private collection of Bohdan and Varvara Hanenko, prominent Ukrainian collectors and philanthropists. The Khanenki have devoted more than 40 years to the creation of the collection. Vienna, Berlin, Paris, Madrid, St. Petersburg, Warsaw, Rome, Florence, even Harbin and probably Cairo are far from a complete geography of the couple's search travels and correspondence with the world's leading art connoisseurs and auction houses. At the beginning of the 20th century, the collection of the Khanenko family was considered one of the best private collections of art and antiquities on the territory of the then empire.

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The breadth of collector interests of the Hanenks is impressive. European painting, sculpture and applied arts of the era of the highest heyday of national schools, rare examples of red art and traditional crafts of West, South and East Asia, art of the ancient world: Egypt, Greece and Rome, Russian and Ukrainian icons, Ukrainian folk art, European and Eastern weapons, unique monuments and whole complexes of archeology, etc.

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During the 1900s, several thousand objects from Khanenka's own collection were donated to the foundations of the first public museum in Kyiv. Today these works are included in the collections of 5 national museums of Kyiv.

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Separate parts of his collection Khanenka published y catalogs of 1899—1907: “B.Y. and V.N. Khanenko. Collection of paintings of Italian, Spanish, Flemish and old schools”, “Russian antiquity. Crosses and Icons”, “The Antiquities of the Transnistria”, issues 1-6. Invaluable evidence of the history of the formation of the collection of European painting is provided by the memoirs of Bohdan Khanenko, elaborated and published by the museum in 2008.

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After the death of Bohdan Khanenko, at the end of 1917 Varvara Khanenko transported several dozen of the most valuable European and Asian works to Kyiv from their Petrograd apartment. The record of the collection during the museification in the spring of 1919 gives the following data: 1259 works. However, this is not the final volume of the Khanenko gathering. In 1921, the director of the museum Nikolai Makarenko returns from Russia to Kiev more than a hundred works donated by the Khanenkas in 1915 for safekeeping to the Historical Museum.

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At the same time, in the early 1920s, works of art from other nationalized noble collections come to the newly created museum: Repnin, Branitsky, Gudym-Levkovych, Sakhnovsky. In 1921, the Asian collection of the museum is replenished with a large (several hundred units) collection of archaeological ceramics of Central Asia of the 9-12th centuries (collection of Mikhail Stolyarov and others). In 1925, by the will of the Petersburg collector Vasily Schavinsky, the museum receives in 1925 a unique collection of works by masters of northern European schools.

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In the Darchy statement of Varvara Khanenko, whose collector in 1918 handed over the priceless collection to the attention of the All-Ukrainian Academy of Sciences, the condition of the gift, in particular, is the “indivisibility” of the donated collection.

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However, history was different. The Ukrainian Soviet cultural elite of the 1920s put forward the idea of a unified museum fund and redistribution of museum collections “by profile”. During the implementation of this idea during the 1920s-1930s, a huge part of the Khanenkov collection was transferred from the museum collection to the funds of other Kiev museums. Family portraits, Ukrainian and Russian icons, painting, graphics, sculpture, furniture, decorative and folk art, various collections of archaeological monuments (“times of migration of peoples”, Byzantium, Russia), a large collection of weapons and armor. The former museum of the “encyclopedic” art collection of the Khanenko has acquired a much narrower profile: the museum of “Western and Eastern art”.

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In 1929-1930, during the Soviet campaign to sell museum treasures abroad, several of the most valuable works of European and Asian art were removed from the museum. However, not everything that was removed was sold. So, the unique Khanenko bronze Aquarius, created in Iran in 1206, was in the funds of the State Hermitage.

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In the second half of the 1930s, the Museum Town on the territory of the Kyiv-Pechersk Lavra transferred to the museum valuable collections of cult art. In 1936 — collection of monuments of religious art of Central Asia and the Far East. 1940 - masterpieces of world importance: 4 early Byzantine encaustic icons of the 6-7 century.

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In the summer of 1941, with the beginning of hostilities on the territory of the Soviet Union, the most valuable part of the museum collection was evacuated to Ufa (then the Bashkir ASSR, now Bashkortostan). From what was left in Kiev, the Nazis took away the most valuable works that were taken out of Ukraine during the retreat of 1943. Today, the museum is making efforts to find and return stolen valuables.

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In the post-war period, the museum collection was enriched with several valuable revenues. In the 1950s, Taisiya Jaspar donated and sold more than 350 works of classical Chinese painting, sculpture and applied arts to the museum. In 1969, the museum bought 41 works of cult art of Buddhism from the collection of the Moscow collector Valerian Velichko. During the 1970s, the museum systematically formed a collection of Japanese netske sculpture (about 70 pieces). The gifts of the 1990s and 2000s from patrons Galina Shcherbak, Vasily Novitsky, Alexander Feldman became valuable contributions to the Asian collection of the museum.

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