[3] Among the museum's highlights are, the Dura-Europos synagogue,[2] a reconstructed synagogue dated to 245 AD, which was moved piece by piece to Damascus in the 1930s, and is noted for its vibrant and well preserved wall paintings and frescoes, as well as sculptures and textiles from central Palmyra, and statues of the Greek goddess of victory from southern Syria.

The first museum was founded in 1919 under the supervision of the Syrian Ministry of Education at Al-Adiliyah Madrasa and housed a smaller collection until this was moved to its current location.

On the facade, it presents the front walls of the Umayyad palace of Qasr al-Hayr al-Gharbi, which was removed from its location in the Syrian Desert.

[10] The discovery of Qasr al-Hayr al-Gharbi adding new attention to the collection of the Islamic period, the Directorate of Antiquities decided to incorporate the fragments of the palace into the museum.

The front façade of the palace was transported to Damascus, before being carefully reconstructed as the National Museum's main entrance.

[12] Some of the museum's unique exhibits are the restored wall paintings of the Dura Europos Synagogue from the 3rd century AD, the hypogeum of Yarhai from Palmyra, dating to 108 AD and the façade and frescoes of the Umayyad period Qasr Al-Heer Al-Gharbi, which dates back to the 8th century and lies 80 km south of Palmyra.

Among other exhibits, there are tablets, cylinder seals and amulets from ancient sites such as Ebla, Mari, Ugarit and sculptures from Tell Halaf.

The displays include sculptures, marble and stone sarcophagi, mosaics, jewelry and coinage from the Seleucid, Roman and Byzantine periods.

[15] The hypogeum, which dates from 108 AD, currently is found in the underground part of the museum, and can be reached after taking the stairs from room 15.