It is one of the five components of the National Museum and currently consists of eight departments: the Mineralogical and Petrological, Paleontological, Mycological, Botanical, Entomological, Zoological, Anthropological, and the Ringing Station.

[2] Kaspar Maria von Sternberg, a versatile naturalist and a leading figure among the founders of the museum, played a significant role in this.

Next to Charles University, the museum was the main center of natural sciences in the Czech lands, and the names of leading natural scientists are closely connected with it (besides Kaspar Maria von Sternberg, August Carl Joseph Corda, Carl Borivoj Presl, Jan Svatopluk Presl, Franz Xaver Maximilian Zippe, Maxmilian Dormitzer, August Emanuel von Reuss, Jan Krejčí, and Antonín Frič).

[4] A distinctive landmark of the zoological exhibitions in the historical building of the National Museum is the 22.5 meters long, over four-ton skeleton of the whale (Balaenoptera physalus).

[5] The complete skeleton was later offered by the Norwegian Whaling Society to European museums for the relatively high price of 2,500 guilders.

The current headquarters of the Natural History Museum is located in the Prague district of Horní Počernice on the site of the former wintering ground of the Czechoslovak State Circus and Variety Theatre.

Currently, there are seven departments of the Natural History Museum in Horní Počernice (excluding the Ringing Station), including depositories and technical facilities.

The collection was built and managed by such prominent personalities as Franz Xaver Maxmilian Zippe and Professor Karel Vrba.

In addition to managing and replenishing the collections, the staff of the Mineralogical and Petrological Department are engaged in research, scientific, and publication activities.

The department staff provides consultations to the public, closely cooperates with the mineralogical section of the Society of the National Museum, and participates in the preparation of exhibitions of natural science and historical interest.

[7] The Mycology Department, which has existed independently since 1965, focuses on building collections, scientific study, popularization, and raising awareness of fungi and lichens.

[8] The botanical collections were based on the extensive European herbarium and the valuable natural history library of Kaspar Maria von Sternberg, one of the museum's founders.

The collections of the Botanical Department comprise over two million herbarium items, liquid specimens, and samples of wood and dried fruits from all over the world.

The department's collections include more than seven million specimens from all over the world and are divided into seven referees according to the zoological system: the straight-winged (Orthopteroid orders), the hemipteran (Hemiptera), the palm-winged (Hymenoptera), the beetles (Coleoptera), the butterflies (Lepidoptera), the dioecious (Diptera), and the so-called "small orders referee" bringing together the remaining less numerous groups.

The research activities of the Entomology Department are mainly focused on fields that cannot do without extensive collections, i.e., systematics, comparative morphology, and zoogeography of various insect groups.

The staff of the department is currently working mainly on systematics, evolution, ecology and biogeography of fish, amphibians, reptiles, birds, mammals and spiders.

Since its establishment, the department has collected about 23,000 skeletal finds or urn graves, which it has obtained mainly from archaeological excavations in the territory of the former Czechoslovakia, later the Czech Republic.

[15] The museum staff organizes or participates in a number of foreign expeditions outside the Czech Republic (e.g., Morocco,[16] Peru,[17] Laos,[18] South Arabia,[19] and Papua New Guinea[20]).

[23] The Natural History Museum has traditionally organized citizen science projects in which the general public participates to a greater or lesser extent in the process of scientific research.

[24] By involving a large number of trained volunteers, naturalists gain a wealth of important data, and participants learn skills about the process of scientific inquiry.

[25] Using the iNaturalist app, interested people take photos of nature in their neighborhood, providing valuable data for professional naturalists.

The Natural History Museum has recently organized or co-organized the following exhibition projects: The results of the research activities of the different departments are presented at conferences and mainly in scientific literature.