A soldier (1895–1904) in the colonial army during the Acehnese War in northern Sumatra, Colijn later served there as a civil administrator, organizing government services and rubber plantations. He entered the Dutch Parliament in 1909 as a member for the orthodox Calvinist Anti-Revolutionary Party and became war minister (1911–13). After serving as director (1914–22) of the company that later became the Royal Dutch Petroleum Company (Shell), he succeeded Abraham Kuyper in 1922 as leader of the Anti-Revolutionary Party and editor of its newspaper, De Standaard.

He served as finance minister from 1923 to 1925. After a brief ministry in 1925–26, he became prime minister again in 1933 and pursued a policy of “adaptation” (reducing the general standard of living) and of postponing devaluation of the currency. He was forced to resign from office in July 1939 after dropping the Catholic bloc from his coalition Cabinet. Having remained in The Netherlands as editor of De Standaard after the German occupation in 1940, he was arrested in July 1941 and spent his remaining years under Nazi supervision.