Designed by British architect Austen Harrison, it blends Western architectural achievements with Eastern influences, using materials such as Turkish nut doors and Armenian ceramics.

[9] Visiting Mandatory Palestine in 1925, James Henry Breasted, founder and director of the University of Chicago's Oriental Institute, recognized the need for an archaeological museum in Jerusalem to house important regional finds.

[9] Encouraged by Lord Plumer, the British High Commissioner, Breasted approached American philanthropist John D. Rockefeller Jr., who agreed to donate two million dollars toward the project.

The museum was designed by Austen Harrison, chief architect of the Mandatory Department of Public Works, who drew up blueprints for a white limestone building integrating eastern and western architectural elements.

[2] The museum's opening was overshadowed by the murder of British archaeologist James Leslie Starkey by local Arabs.

[16] After the 1948 Arab–Israeli War, the museum also became a secondary headquarters of the Jordanian Department of Antiquities, headed by Gerald Lankester Harding until 1956.

The museum's first curator was John H. Iliffe,[19] who arranged the artifacts in chronological order, from two million years ago to 1700 AD.

Among the museum's prized possessions are 8th-century wooden panels from the Jami Al-Aqsa and 12th-century (Crusader-period) marble lintels from the Church of the Holy Sepulchre.

One of the Lachish letters is on permanent display at the museum,[21] as are the statuary and stucco decorations from the Umayyad Hisham's Palace.

It includes the largest of the Beisan steles (considered "the most impressive find from Egypt's rule over Canaan")[22] a 9,000-year-old statue from Jericho (one of the oldest representations of a human figure ever found), as well as gold jewelry from the Bronze Age.