After the beginning of the Eastern Front (World War II), the most valuable and unique exhibits were evacuated to the city of Ufa (Bashkortostan). They were returned to Kyiv in 1947. 

The archaeological and ethnographic collections that remained in Kyiv were moved to the Pedagogical Museum (now the Kyiv City Teacher's House). Other museum collections were transferred to the Ukrainian Museum on the Oleksandrivska Street.

In 1942, the archeological museum was headed by the German archaeologist Paul Grimm, his deputy was the famous Ukrainian archaeologist Petro Kurinnyi. In 1942–1943, the museum was called the Regional Museum of Pre- and Early History. A significant part of valuable museum exhibits was transported to Germany in 1941 and 1943.

After the entry of Soviet troops into Kyiv, the museum resumed its work in November 1943. The museum was located on the premises of the Teacher's House, separate collections were stored in other places in Kyiv.

In May 1944, the museum was placed on the premises where it still works, i.e. the 2 Volodymyrska Street, in the building of the former art school.

The main facade of the building is designed in classical forms and opens to the site in front of the museum, while the rear, viewed in the panorama of Starokyivska Mountain, resembles Byzantine monumental buildings.

In the post-war years, the museum staff faced the difficult task of systematizing the re-evacuated materials. The museum was opened to visitors only in 1948.

As a result of the war, the museum collection has undergone dramatic changes — a significant number of unique exhibits were lost. Then, the collection was replenished at the expense of other museums such as Lviv Historical Museum, Lviv Museum of Ukrainian Art, Odessa Archaeological Museum, National Art Museum of Ukraine, St. Sophia Cathedral, Kyiv-Pechersk Lavra (Kyiv Holy Dormition Caves Lavra), Chernihiv Historical Museum.

According to the decree of the Council of Ministers of the Ukrainian Soviet Socialist Republic dated November 22, 1963, a special department "Zolota Komora" (Golden Chamber) was created at the museum, which since 1965 has been functioning as a branch of the museum.

The funds of the historical museum became the basis for the creation of other branches — the "Liberation of Kyiv From Nazi Invaders" museum (now the National Museum-Preserve "Battle for Kyiv 1943"); Kosyi Kaponir Museum (now Kyiv Fortress Museum). The Ukrainian State Museum of the Great Patriotic War of 1941-1945 (now the National Museum of the History of Ukraine in the Second World War) was created based on the museum's funds (25,000 exhibits).

In the era of "Brezhnevian stagnation", the museum staff focused on collecting materials related to the so-called achievements of the Soviet state. These were labor reports of collectives, socialist commitments, complexes of Soviet heroes, pennants, flags, and documents of party congresses, etc. The museum was designed to promote the achievements of socialism, revealing the leading and guiding role of the CPSU (Communist Party of the Soviet Union).

After the restoration of Ukraine's state independence and by the resolution of the Cabinet of Ministers of Ukraine dated October 15, 1991, the State Historical Museum of the Ukrainian Soviet Socialist Republic was renamed the National Museum of the History of Ukraine.

Nowadays, the National Museum of the History of Ukraine is one of the leading museums of Ukraine in terms of the number and value of its collections. Its fund collections include more than 800,000 exhibits. These are world-important archaeological and numismatic collections, ethnographic collections, collections of weapons, monuments of decorative and applied art, manuscripts, old prints, works of painting and graphics, and relics of the Ukrainian national liberation movement of the 20^th century. They reflect the history of Ukraine from ancient times to the present.

In October 2020, the museum underwent a rebranding, developed by the creative agency TABASCO. One of the important elements of the rebranding is acronyms: Museum of History = MIST (Музей ІСТорії = МІСТ). The graphic sign of the logo – the letter M – symbolises that it is in the MIST (literally «bridge» in Ukrainian) that the past and the future meet, where civilisations and knowledge unite. Our MIST (as a bridge) connects not only epochs but also people. The museum can discover the history of Ukraine for Ukrainians and the world, making it more understandable and encouraging a deeper acquaintance with the country.

After the full-scale Russian invasion in February 2022, the museum's exhibits and its branches were dismantled and evacuated. Instead, the museum implements temporary exhibition projects. Some employees joined the ranks of the Armed Forces of Ukraine. Currently, researchers are engaged in collecting materials of the Russian-Ukrainian war.

A branch of the institution is the Treasury of the National Museum of the History of Ukraine (formerly the Museum of Historical Treasures of Ukraine), where unique materials from precious metals and precious stones are collected. Masterpieces from the collection of the Scythian period, products of masters of the Princely era (Kniazha Doba), and works of Ukrainian jewelers of the 14^th-20^th centuries are of particular value. The collection of Jewish cult silver from the early 19th century is known in Ukraine and abroad.