The palace, founded at the end of the 17th century, is the work of the most famous architects and artists working in the Grand Duchy of Lithuania: Giambattista Frediani designed the palace, while sculptor Giovanni Pietro Perti and painter Michelangelo Palloni decorated it.

The Baroque palace lost its original appearance when the building was converted into a hospital between 1843 and 1848. Based on the principles of the Venice Charter (1964) and other international conservation documents, it was decided to return the Sapieha Palace to the appearance of the 1692 project.