At the first Zionist Congress in Basel in 1897, Professor Herman Schapira suggested the establishment of a Jewish University. The idea was positively received, but the Zionist movement was too young to take practical steps towards the execution of the idea. Four years later, at the Fifth Congress, Chaim Weizman made a similar proposal. In 1902, Weizman, Martin Buber, and Berthord Feiwel, published a pamphlet called Eine Judische Hochschule ( A Jewish College) , detailing plans to create such a University. At the Eleventh Congress which met in 1913, Chaim Weizman and Menachem Usshikin pushed hard for the project, and the Congress resolved to take immediate steps to create the University. In 1919, the Gray Estate on Mt. Scopus was purchased and the cornerstone was laid. Three separate departments were established; one for chemistry, one for Jewish physicians, and a third for Jewish studies. On April 1, 1925, the University was inaugurated with a gala celebration presided over by Sir Herbert Samuel, Hayim Bialik, and Rabbi Abraham Kook. The guest speaker was the Earl of Balfour, the author of the Balfour Declaration.

The University expanded rapidly and became one of the major institutions of higher learning in the Middle East. The Mt. Scopus campus was cut off from the rest of Jerusalem during the War of Independence, and for several years the University operated out of scattered buildings in West Jerusalem. In 1953, the Givat Ram campus was inaugurated. With the reunification of Jerusalem in 1967, the Mt. Scopus campus was rebuilt and today is once again a major center of learning. Today the University is the leading University in Israel with 350 departments. Over 1/3 of all Ph.D. students in Israel study at Hebrew University.