While continuing his self-education, Nash worked as a costing clerk around Birmingham and became a wholesale confectionery merchant in 1907. He emigrated to New Zealand in 1909, soon joining the Labour Party, and from 1919 to 1960 he was a member of the party's executive. He entered Parliament in 1929 and became the first Labour minister of finance in 1935. In 1938 he was named to head the newly formed social security program, which provided guaranteed medical care and improved pensions.

Nash was deputy prime minister from 1940 to 1949. During World War II he introduced a program to control prices, wages, and costs; raise taxes; impose rationing; and increase family welfare benefits—a program under which New Zealanders experienced a smaller decline in their standard of living than did the peoples of other Allied nations. From 1942 to 1944 Nash also served as New Zealand's minister to the United States and as a member of the Pacific War Council. He was a delegate to the United Nations financial conference at Bretton Woods, N.H. (1944).

After leading the Labour Party opposition in Parliament during 1950–57, Nash served as prime minister and minister of external affairs and Maori affairs (1957–60). He headed the Labour opposition again from 1960 to 1963. In foreign policy, he opposed the United States' involvement in Vietnam and favoured the seating of the People's Republic of China in the United Nations. Nevertheless, he supported New Zealand's defense treaties with the United States. He was knighted in 1965.