After joining the Labor Party in 1903, Scullin served in Parliament (1910–13) and edited a Labor newspaper, the Echo, during World War I. Elected to Parliament again in 1922, he became leader of the party in 1928 and helped it become stronger than it had been since its split in 1916. When he became prime minister in 1929, he was immediately confronted with the economic depression, compounded by opposition control of the Senate, noncooperation by the Commonwealth Bank of Australia, and inexperience in his Cabinet.

Scullin's deflationary measures (wage decreases, rationing, limitations on imports, and attempts to balance budgets) initially were successful. But after his treasurer, Edward Granville Theodore, was forced to resign in July 1930 following a mining scandal in Queensland, the Cabinet split on financial policy. Scullin's support of Theodore's return to the Cabinet in 1931 and of a plan to expand credit divided the party and led to his defeat in the 1931 elections.

Scullin led the Labor opposition from 1932 to 1935 and retired from Parliament in 1949.