During World War I, he volunteered for the Jewish Legion of the British Army, and joined the group which founded the settlement of Degania Beth. Eshkol later worked in the Histadrut Labor Federation's Agricultural Center. He participated in the establishment of "Mekorot," Israel's water utility, in 1937, and served as its chief executive until 1951.

In 1947 he organized the recruiting drive for what became the Israel Defense Forces. With the establishment of the State he became the first Director­General of the Ministry of Defense. He also became the head of the World Zionist Organization/Jewish Agency's Settlement Department (WZO/JAFI) in 1948. In 1951 Eshkol was appointed Minister of Agriculture and Development and from 1952 until 1963 he served as Minister of Finance. He remained Chairman of the WZO/JAFI Settlement Department until 1963. In June 1963, Eshkol assumed the post of Prime Minister. The high point of his premiership was the Six Day War of June 1967.

Eshkol died in office on February 26, 1969 of a heart attack.