Born to a Hasidic family of the Chabad-Lubavitch stream in Mir, near Minsk, he received a religious education as a youth. In his teenage years he became involved in the Poale Zion Movement. Shazar immigrated to Mandate Palestine in 1924, and became a member of the secretariat of the Histadrut.
Shazar also served as the editor-in-chief of the Israeli newspaper Davar from 1944 to 1949. He was elected to the first Knesset in 1949 as a member of Mapai, and was appointed Minister of Education in David Ben-Gurion's first government. He was not a member of Ben-Gurion's second cabinet, but retained his seat in the 1951 and 1955 elections. He also became a member of the Jewish Agency Executive in 1952. He resigned from the Knesset in 1956, and from 1956 to 1960 was acting chairman of the Jewish Agency's Jerusalem Executive.
His portrait is printed on the 200 NIS bills.
In 1969, Shazar sent one of 73 Apollo 11 Goodwill Messages to NASA for the historic first lunar landing. The message still rests on the lunar surface today. It states, "From the President of Israel in Jerusalem with hope for 'abundance of peace so long as the Moon endureth' (Psalms 72,7)."