Malan was born in the village of Riebeek-Wes.
In 1905, Malan was ordained as a minister of the Nederduits Gereformeerde Kerk and then traveled for several years as a preacher throughout South Africa, the Belgian Congo and Southern Rhodesia.
Malan's political career started in July of 1915 when he joined the National Party and became the first editor of its newspaper Die Burger. The paper actively supported Nationalist causes. Becoming the leader for the National Party in the Cape of Good Hope area, Malan was elected to Parliament in 1918. He had also, by this time, become a member of the Afrikaner Broederbond.
The National Party came to power in 1924, under the leadership of James Barry Munnik Hertzog. Under Herzog, Malan was given the post of Minister of the Interior, Education and Public Health in 1924 – a post he held until 1933. In 1925 Malan was at the forefront of a campaign to replace Dutch with Afrikaans in the constitution.
In 1934, Malan left the government, objecting to the merger between Herzog's National Party and the rival South African Party of Jan Smuts to form the United Party. For the next fourteen years, he was to lead the rump of the National Party in opposition. Malan's opposition to South African participation in World War II, which was unpopular among the Afrikaaner population, dramatically increased his popularity, and in 1948, he defeated Smuts and the United Party. Forty-one years of apartheid followed.
In 1954, at age of 80, Malan retired.