It was built as a railway station and terminus of the Southern Line of Thailand's national rail network from 1903 to 1999; closed in 2003; and renovated and reopened as a museum in 2013.

The original building was designed by German architect Karl Döhring in the style of European brick expressionism.

During World War II, the station became strategically important as the Japanese base of operations for supplying the construction of the Burma Railway.

The ownership of the station and its grounds was subsequently transferred to the Siriraj Hospital Faculty of Medicine to serve as the site of the Sayamindradhiraj Medical Institute.

The museum's exhibits include those regarding the area's origins as the palace of Prince Anurak Devesh, who served as Rear Palace during the reign of King Phuttha Yotfa Chulalok, the building's former role as railway station, as well as the foundation of Siriraj Hospital and its medical school.