Its history dates from the existence of a chapel dedicated to Saint Clement in the 11th century. A Dominican monastery was founded in the medieval period, which was transformed in 1556 to a Jesuit college. In 1622 the Jesuits transferred the library of Charles University to the Klementinum, and the college was merged with the University in 1654. The Jesuits remained until 1773, when the Klementinum was established as an observatory, library, and university by the Empress Maria Theresa of Austria.

The National Library was founded in 1781 and from 1782 the Klementinum was a legal deposit library. In 1918 the newly-established Czecho-Slovak state took over the library. Since 1990, it has been the National Library. It contains a collection of Mozartiana, material pertaining to Tycho Brahe and Comenius, as well as historic examples of Czech literature. The architecture is a notable example of Baroque architecture and Clementinum, covering 20,000 square metres, is the second largest complex of buildings in Prague after the Prague Castle.

For several years before 2006, there was an on-going debate on the possibilities of expanding the space for future library collections, as the room in the current Clementinum buildings is expected to reach its limit by 2010. On Jan 10, 2006, the Prague authorities decided to sell the city-owned property located in the area of Letná near the Prague center, to the National Library. In Spring 2006, an international architectural design competition for the new building was put up. An architect who won the competition is Jan Kaplický, but his winning was infirmed, so the Czech National Library is still waiting for its final project.At one time the Clementinum was known as the third largest Jesuit college in the world.