Founded in 1949, it depicts the life, work and legacy of Vuk Stefanović Karadžić (1787–1864), the reformer of the Serbian language, and Dositej Obradović (1742–1811), a writer who was the country's first Minister of Education.

[6] Under the name Area around Dositej's Lyceum, the neighborhood surrounding the building was placed under the state protection as the spatial cultural-historical unit.

Vuk's collection was established in the late 19th century, when his daughter Mina Karadžić-Vukomanović donated his legacy to the kingdom of Serbia.

[10] Exhibits include objects that belonged to the writer (travel bags, glasses, stilt, rod, holster, smoking accessories), various documents transferred from the Serbian Academy of Sciences and Arts (diplomas, business cards, bills, vouchers), portraits, correspondence and a number of books from his personal library, including a copy of John Bowring's English translation of Vuk Karadžić's poetry from 1827.

The museum occasionally organizes lectures, with the participation of eminent scholars, writers and historians, as well as musical and dramatic artists.

Since 1958, the museum is publishing an annual publication, entitled "Small Case", which is composed of materials and contributions of both Dositej Obradović and Vuk Karadžić, and their followers.

Besides the "Small Case" journal, the museum is distributing other publications, such as guides, monographs and catalogs of thematic exhibits, published both in Serbian and English.