Sharett moved to Palestine from the Ukraine in 1908 and was one of the founding families of the city of Tel Aviv. After World War I he worked for the Palestine Jewish Community's Representative Council. He was a member of "Achdut Ha'Avoda" (Unity of Labor) and later of "Mapai" (Israel Workers' Party). From 1922 to 1924, Sharett was active in "Poalei Zion" (Workers of Zion). He became deputy editor of the Davar newspaper until 1931, when he was appointed Secretary of the Jewish Agency's Political Department.

From 1933 until 1948, Sharett was the Zionist movement´s chief negotiator with the British. Though incarcerated by the British for four months, he established the British Army's Jewish Brigade in 1944, which subsequently provided a postwar lifeline and route to Palestine for many European Jews.

Sharett became Israel's first Foreign Minister in 1949, succeeding Ben-Gurion as Premier in 1954. Sharett yielded the post of Prime Minister to Ben-Gurion in 1955, but remained Foreign Minister until June 1956. Upon retirement, he became the head of the "Am Oved" (Working Nation) publishing house, Chairman of Beit Berl College and representative of the Labor Party at the Socialist International. In 1960 he was elected chairman of the World Zionist Congress and the Jewish Agency.