Born in Poltava, Ukraine. During the 1905 pogrom, he became active in Jewish self­defense and played a leading role in Po'alei Zion, a Zionist socialist organization.

Ben-Zvi settled in Palestine in 1907 and was a Po'alei Zion delegate to the Eighth Zionist Congress. He co-founded the HaShomer Jewish defense organization and the first Hebrew socialist periodical Ahdut (1910). Deported with Ben-Gurion together they founded the He-Halutz (Pioneer) movement of America to prepare young Jews for settlement in Palestine. He returned to Palestine in 1918 as a soldier in the Jewish Legion. During the Arab riots in the 1920's, Ben-Zvi was active in the Hagganah. Ben-Zvi was elected to the leadership of Va'ad Le'ummi first as a member, later as chairman (1931), and finally as president (1945). He founded (1948) and later lead the Institute for the Study of Oriental Jewish Communities in the Middle East, which was later reamed to the Ben-Zvi Institute.

Ben-Zvi was elected President of the State in 1952, and in 1957 was returned to that office for five more years. In 1962 he was elected president for a third term and died in office on April 23, 1963.