The Museum of Litomyšl was founded in 1891 and it was located in the premises of disestablished municipal realschule. Generally it focused on history with orientation on the town and its surroundings. In 1926 the Museum moved to a large Baroque building of former Piarist grammar school, which was built in 1714-1718. Also Mr. Alois Jirásek was teaching at this grammar school, which became later a state school. The Museum has the seat in this building even nowadays and you can find here the permanent exposition and spaces for short-term exhibitions.
Since 1990s the Museum runs also the Native Flat of Bedřich Smetana.
In 2004, existing Municipal Museum changed to the Regional Museum operating on the area of the Svitavy district and the Region of Pardubice became its founder. In the same year the Municipal Gallery of Litomyšl disaffiliated from the Museum and passed over to the municipal government.
Since 2016 the Museum runs also the Portmoneum - Museum of Josef Váchal.