The Museum is located in the historical edifice which previously housed the Great School, which was opened as a lyceum in 1808 by the great Serbian enlightener and the first Serbian Minister of Education Dositej Obradović. A modest collection of his belongings, including personal effects, library and manuscripts, is displayed on the ground floor.

At some point, the Serbian government bought the personal belongings of Vuk Karadžić from his daughter Mina Vukomanović. All personal effects and family belongings of Vuk Karadžić from the National Museum were transferred here, along with the part of his belongings from the Serbian Academy of Sciences and Arts - diplomas, calling cards, various notes, receipts and recipes.